Always Available

Welcoming addresses by :

Alexandre Reymond, President of the ESHG

Joris Veltman, Chair of the Scientific Programme Committee

View an outline of highlights of the day presented by an SPC member.

Educational Sessions

Chair:   Martin Kircher & Malte Spielmann
Virtual Session Room 1

E01.1 Manifold destiny: exploring genetic interactions in high dimensions through massively parallel single cell RNA-seq

Jonathan Weissman;
United States

E01.2 Nanopore Sequencing of Human Genomes: the long and short of it.

Matthew Loose;
United Kingdom

E01.3 Massively Paralleled Variant Interpretation

Douglas M. Fowler;
United States

E01.4 Optical mapping for clinical structural variants detection

Alexander Hoischen;
The Netherlands

E02.1 Reproducibility in Life Sciences

John Ioannidis;

E02.2 Classic misconceptions in high-throughput data analysis and how to learn from them

Bernhard Renard;

E03.1 Pharmacogenetics – From Bench to Drug Label

Julija Stingl;

E03.2 Pharmacogenomic testing in clinical practice

Richard Turner;
United Kingdom

E04.1 Ehlers Danlos Syndromes and the Differential Diagnosis of Hypermobility

Franziska Malfait;

E04.2 Vascular Presentation of the Ehlers Danlos Syndromes

Peter Byers;
United States

E05.1 Functional Characterization and Therapeutic Targeting of Gene Regulatory Elements

Nadav Ahituv;
United States

E05.2 Dissecting and Understanding Non-Coding Sequences

Alexander Stark;

E06.1 Microcephaly

Grazia M.S. Mancini;
The Netherlands

E06.2 Macrocephaly

Ghayda Mirzaa;
United States

E07.1 Editing the Mammalian Genome: Targets and Tools

Helen O’Neill;
United Kingdom

E07.2 Genome-Wide CRISPR-Cas9 Screening in Immune Cells

Pavel Tolar;
United Kingdom

E08.1 What Was, What Is, What If – Trends and Predictions In Assessing Genetic Counseling

Robert Resta;
United States

E08.2 How to help society interact with genomic technology

Anna Middleton;
United Kingdom

E09.1 Diagnostic Approach Update in Mitochondrial Disease

Marni Falk;
United States

E09.2 The Origin of mtDNA Mutations: Population Genetics and Disease – CANCELLED

Patrick Chinnery ;
United Kingdom

E10.1 Gene therapy in genetic disorders

Marina Cavazzana;

E10.2 Trial readiness, trial endpoints and stakeholder collaboration

Volker Stauber;
United Kingdom

E11.1 Heritability Estimation and Gene-Environment Interactions

Alexander Young;
United Kingdom

E11.2 Flexible Heritability Estimation from Summary Statistics

Doug Speed;

E12.1 A Guide to Deep Learning in Healthcare

Mark DePristo;
United States

E12.2 Challenges and chances for deep learning in medical applications

Marcel Schulz;

E13.1 Mitochondrial replacement techniques: Exploring the biological consequences

Mary Herbert;
United Kingdom

E13.2 Should the UK’s Approach to MRT be Adopted in Other Countries? – CANCELLED!

César Palacios-González;
United Kingdom

E14.1 Recent Advances in the Identification and Characterization of Expanded Repeats

Paul J. Lockhart;

E14.2 Therapeutic advances in Huntington’s disease with relevance to other repeat expansion disorders

Sarah J. Tabrizi;
United Kingdom

E15.1 Variant Interpretation in Hereditary Colorectal Cancer Syndromes: Lessons Learned from INSIGHT

Maurizio Genuardi;

E15.2 Variant interpretation in Hereditary Breast and Ovarian Cancer Syndrome Patients: Lessons Learned from ENIGMA, ClinGen and Other International Consortia

Fergus Couch;
United States

E16.1 Optimising access to genetic services for consanguineous families: The UK experience – CANCELLED!

Naz Khan;
United Kingdom

E16.2 Consanguinity and endogamy in health and disease

Hilary Martin;
United Kingdom


Workshop Organiser: Kaitlin Samocha

About the workshop:

Although exome sequencing is now routinely available both for research and clinical purposes, the interpretation of identified variants remains a major challenge. In this workshop, we will discuss publicly available resources to aid in variant interpretation from exome sequencing, methods to make the most of exome sequencing data, and lessons learned as part of the 100,000 Genomes Project. We will finish with real-life examples from clinical cases.

Detailed programme:

DECIPHER Workshop (15 minutes)
Julia Foreman

Recyling your exomes (15 minutes)
Christian Gilissen

The highs and lows of whole genome sequencing for rare and inherited disorders in the 100,000 Genomes Project (15 minutes)
Ellen Thomas

Clinical Cases (15 minutes)
Katrin Ounap

Workshop Organiser: Birte Zurek, Olaf Rieß, Holm Gräßner

About the workshop:

“Solve-RD – solving the unsolved rare diseases” is a research project funded by the European Commission for five years (2018-2022) aiming at improving the diagnostic and therapeutic management of rare diseases. It will deliver seven implementation steps, including one dedicated to treatment as part of the “genetic knowledge web”. With this in mind, we propose a method of allowing clinicians to access this information promptly to benefit patients affected by rare disease and their families. The “Treatabolome” is an evidence-appraised database of rare diseases treatments for specific genes and variants to be made available through genetic diagnosis and support tools, for example, the Genome-Phenome Analysis Platform of RD-Connect. The Treatabolome aims at contributing to raising awareness and increasing the visibility of existing rare diseases’ treatments to clinicians.

Detailed programme:

Concept of Treatabolome (15 minutes)
Gisèle Bonne (Sorbonne Université-Inserm, Centre de Recherche en Myologie, Paris, France)

Writing Systematic Reviews to produce FAIR compliant therapeutic datasets (15 minutes)
Rachel Thompson (Children’s Hospital of Eastern Ontario Research Institute, Ottawa, Canada)

A Medical Action Ontology (MAxO) for Therapies and Medical Management of Rare-Disease Patients (15 minutes)
Peter Robinson (The Jackson Laboratory, Farmington, CT, United States)

Building a treatabolome database (15 minutes)
Sergi Beltran and Leslie Matalonga (Centre Nacional d’Anàlisi Genòmica (CNAG-CRG), Barcelona, Spain)

Workshop Organiser: Vita Dolžan

About the workshop:

Pharmacogenomics has the potential to make pharmacotherapy safer and more effective by utilizing patient’s genetic data for drug selection and dosing. However, the implementation of pharmacogenomic testing in clinical practice is slow and facing some challenges that will be discussed during the workshop. Examples of successful integration into routine clinical care will also be presented along with some typical cases where pharmacogenomics played a role in a real world clinical practice. These examples will be used to pinpoint to some challenges and also limitations of pharmacogenomic testing in order to pave the way for a rational use of pharmacogenomics in the clinical practice.

Detailed programme:

Introduction: Pharmacogenomics in translation from research to practice: the lessons learnt from the UPGx project (15 minutes)
Vita Dolžan

Pharmacogenomics from lab to clinic: Pharmacogenomics passport (20 minutes)
Ron Van Schaik

Pharmacogenomics – cases from real world precision medicine (20 minutes)
Julia Carolin Stingl

Conclusions (5 minutes)
Vita Dolžan

Workshop Organisers:  Danya Vears, Gabriel Lazarin

About the workshop:

In this workshop, we propose to articulate challenges and innovative solutions to:

1) pre-test education and informed consent
2) results disclosure to patients
3) communication of results to family members

By including speakers with both a research and practical focus on genetic counselling and test delivery, we also aim to illuminate multiple approaches to addressing these. We will encourage critical analysis and discussion of these approaches to gain understanding of their effectiveness and replicability.

Detailed programme:

Introduction (5 minutes)
Danya Vears, Gabriel Lazarin

Innovations in recontacting: first results of a randomized trial using a digital platform (15 minutes)
Irene van Langen (University Medical Center of Groningen, The Netherlands)

Edna: How can a chatbot augment genomic counselling for Additional Findings? (15 minutes)
Dana Bradford (Australian E-Health Research Center, Australia)

Technology-Driven Prenatal Screening Results Disclosure and Management (15 minutes)
Aishwarya Arjunan (Myriad Women’s Health, United States)

Conclusion (10 minutes)
Danya Vears, Gabriel Lazarin

Workshop Organisers: Celia Azevedo Soares, Florence Riccardi, Ruta Marcinkute  & Patricia Calapod
Virtual Session Room 1

About the workshop:

In recent years there has been a special interest of the younger human geneticists in organizing events that focus on their interests. With this aim in mind the ESHG Young Board and Young Geneticist Network (YGN) are organizing their first collaborative session during the ESHG 2020 Virtual Conference with a focus on themes related to professional development for young human geneticists.

Previously to ESHG 2020, the YGN community voted, on Facebook social media, for one topic to be discussed at this session and the selected topic was: Human Genetics in different countries. Two additional topics, selected by the organization of the workshop, will be discussed by a guest speaker.


by the workshop organisers

Work-life balance: how to have it all
Marni J. Falk
Executive Director, The Children’s Hospital of Philadelphia Mitochondrial Medicine Frontier Program
Associate Professor, Division of Human Genetics, Department of Pediatrics, University of Pennsylvania Perelman School of Medicine

ERN: Opportunities for the next generation
Alain Verloes
Medical Genetics Department, Hôpital Robert DEBRE, Paris Public University Hospital (AP-HP)
European coordinator of ERN ITHACA (Intellectual Disability and Congenital Malformations).

Public choice – Human Genetics in different countries
Sofia Douzgou
Education and Training Lead, NW Genomic Laboratory Hub

Workshop Organisers: Carla Oliveira, Conxi Lazaro
Virtual Session Room 2

About the workshop:

SCOPE: This workshop is about European Reference Networks (ERNs), which are virtual networks involving healthcare providers across Europe. They aim to facilitate discussion on complex or rare diseases and conditions that require highly specialized treatment, and concentrated knowledge and resources.

AIM: The workshop is aimed at presenting and raising awareness about the first European guidelines on heritable TP53-related cancer syndrome (formal Li-Fraumeni syndrome) and PTEN hamartoma tumour syndrome, recently published by the ERN GENTURIS members in EJHG. A general discussion with the audience is expected about guideline implementation in Europe and at the National level.

AUDIENCE: Health Professionals and Scientists working in the field of Human Genetics in Europe, mainly in the Hereditary Cancer context.

Attendees will learn about:

-The first European guidelines on heritable TP53-related cancer syndrome (formal Li-Fraumeni syndrome).
-The first European guidelines on PTEN hamartoma tumour syndrome.
-Strategies for guideline implementation in Europe and at the National level.


Carla Oliveira, Conxi Lazaro

Guidelines for the Li-Fraumeni and Heritable TP53-Related Cancer syndromes
Thierry Frébourg, Rouen University Hospital, Rouen, France

Guidelines for the PTEN hamartoma tumour syndrome
Marc Tischkowitz, Cambridge University Hospital, Cambridge, United Kingdom

Round Table, Q&A
All participants in the session

Session Closing
Carla Oliveira, Conxi Lazaro

Workshop Organiser: Robert Kuhn
Virtual Session Room 3

About the workshop:

The UCSC Genome Browser offers data and many visualization features to help the scientist get the most out of large genomic datasets. This virtual workshop will touch a few things that are useful in the Browser and not always discovered by the casual visitor.

1. The GTEx dataset presents transcription profiles for every human gene across a large number of tissues. The data are presented in the Browser as both a normalized dataset, averaging all transcripts of a gene locus and also as a transcript-specific dataset, making it possible to identify specific transcripts that may be expressed in a tissue of interest. A variant in a gene may become interesting if the researcher can identify an appropriate isoform/tissue combination.

2. Scientists can load their own expression data into the Genome Browser in the same barChart format as is used in the GTEx datasets. We will demonstrate how to display data in this format. It is an excellent way to summarize expression data that may cover a large number of tissues or treatments in a coherent visualization.

3. The Saved Sessions feature of the Browser is used to store and share sessions for future use. For example, a clinician may have a certain location and combination of datasets configured to tell a story about a patient sample and can save that configuration for easy access when discussing the case with the patient or colleagues. This and other sessions, saved for different purposes can be used to easily access important information.

4. The UCSC team typically focuses on human, mouse and other vertebrate genomes, particularly in service of comparative genomics and the things that can be learned by exploring homologies across the animal kingdom. However, in light of the recent global coronavirus situation, we have also built a genome browser on the SARS-CoV-2 genome, including proteomics, gene models and comparative datasets on variants around the world:

Virtual Session Room 1

Workshop Organisers:  Nicole de Leeuw, Erica Gerkes

About the workshop:

Various aspects of copy number variant (CNV) interpretation and classification in a diagnostic setting will be discussed in this interactive session. Data including multi-, intra- and intergenic CNVs detected by either genome wide array analysis or in Whole Exome/Genome Sequencing data will be presented.

The aim of this workshop is to focus on various aspects of copy number variant (CNV) interpretation and classification in a diagnostic setting. We will talk about multi-, intra- and intergenic CNVs detected by genome wide array analysis, but also CNV detection in Whole Exome/Genome Sequencing data will be included. We will use illustrative cases from our own diagnostic laboratories to have an interactive discussion on the more challenging findings, including reduced-penetrant, recurrent CNVs, noncoding CNVs and structurally rearranged chromosomal imbalances as well as patients with compound heterozygous variants in a recessive disease gene.

Participants are encouraged to send questions, comments or suggestions related to this topic by e-mail to before June 6, 2020.

Detailed programme:

Nicole de Leeuw, University Medical Center Nijmegen, Netherlands

Broadening our diagnostic view on copy number variants
Nicole de Leeuw, University Medical Center Nijmegen, Netherlands

The (un)usual suspects
Erica Gerkes, University Medical Center Groningen, Netherlands

Concluding remarks
Erica Gerkes, University Medical Center Groningen, Netherlands

Virtual Session Room 2

Workshop Organiser:  Dieter Beule

About the workshop:

The workshop will discuss concepts and tools enabling more medical trained users in the analysis of whole exome variant data sets from individuals, families and cohorts. We will demonstrate how to efficiently filtrate and prioritize variants for different biomedical questions using inheritance, quality metrics, disease gene panels and phenotypic information and furthermore discuss data quality control as well as workflow validation.

Workshop speakers:

Introduction to the Workshop
Dieter Beule, Berlin Institute of Health

Collaborative and Comprehensive Variant Analysis Platform for Translational Research (including demo of VarFish and SODAR software)
Manuel Holtgrewe, Berlin Institute of Health

How to validate Whole Exome Diagnostics
Ben Liesfeld, Limbus Medical Technologies GmbH, Rostock

HPO-Based Search for Disease Mutations: Advantages, Drawbacks and Alternatives
Dominik Seelow, Charité – Universitätsmedizin Berlin

A clinician’s guide to PanelApp
Ellen Thomas, Genetics England

Closing Remarks
Dieter Beule, Berlin Institute of Health

Virtual Session Room 3

Workshop Organiser:  Michal Szpak

Interpreting genetic variation in clinical research using Ensembl: exploring Ensembl/GENCODE annotation, MANE transcripts and the Ensembl Variant Effect Predictor

About the workshop:

The Ensembl/GENCODE geneset ( of protein coding genes, pseudogenes and lncRNAs on the human and mouse genomes is produced by expert manual annotation. Recently, Ensembl has joined with NCBI’s RefSeq team to produce the Matched Annotation from NCBI and EMBL-EBI (MANE) transcript set.

The aim is to generate a genome-wide set that:
1) aligns to GRCh38,
2) includes pairs of 100% identical Ensembl/GENCODE (ENST) and RefSeq (NM) transcripts and
3) is well-supported.

We envision this dataset serving as a unified high-value reference set for consistent reporting of genetic variation as well as for comparative genomics and basic research. This workshop will take you through the annotation process for Ensembl/GENCODE and MANE, allowing you to experience the challenges and conflicts involved in annotation and transcript selection. You will use use Ensembl’s Transcript Archive tool (Tark) to explore comparisons of different isoforms, versions and database sources for transcripts. You will also learn to use the popular Ensembl Variant Effect Predictor (VEP) to map genetic variants onto Ensembl/GENCODE transcripts, determine their likely effects and filter to find candidate variants.

Workshop speakers:

Michal Szpak, EMBL-EBI
Joannella Morales, EMBL-EBI
Adam Frankish, EMBL-EBI
Andrew Parton, EMBL-EBI
Jonathan Mudge, EMBL-EBI
Bethany Flint, EMBL-EBI
Jane Loveland, EMBL-EBI

Virtual Session Room 4

Workshop Organisers:  Anton Nekrutenko, Marius van der Beek

About the workshop:

The goal of the workshop will be to demonstrate the utility of the Galaxy platform for analysis of large numbers of human samples. In this workshop we will use Galaxy and all currently available human metatransciptomic COVID-19 sequencing data to perform genomic analyses of human transcriptomic responses to the coronavirus infection.

This is will include:
– Identification of sequence variants in both host (diploid variant calling) and CODIV-19 (pooled calling)
– Analysis of transcriptome responses including the effect of COVID-19 on human unfolded protein response
– Analysis of coronavirus-related RIBOseq data
– Analysis of human Permanganate-seq data

The outcome of the workshop: Participants will learn how to use worldwide Galaxy instances to analyze multiple types of sequencing data including DNAseq, ChIPseq, RiboSeq, and RNAseq generated with Illumina, Oxford Nanopore, and Pacific Biosciences platforms.

Workshop speakers:

Anton Nekrutenko
Marius Van Den Beek

Plenary Sessions

Chairs:   Alexandre Reymond, Joris Veltman
Virtual Session Room 1

PL1.1 Title to be announced

Speaker to be announced;
This lecture will be given by the Leena Peltonen Prize Award Winner.

PL1.2 RNA splicing defects in cancer

Robert Bradley;
United States

PL1.3 Molecular therapy for Cystic Fibrosis

Harry Heijerman;
The Netherlands

Chairs:   Alexandre Reymond, Joris Veltman
Virtual Session Room 1

PL2.1 Evaluation of DNA methylation episignatures for diagnosis and phenotype correlations in 42 Mendelian neurodevelopmental disorders

E. Aref-Eshghi, J. Kerkhof, V. Pedro, Groupe DI France, M. Barat-Houari, N. Ruiz-Pallares, M. Alders, M. Mannens, P. Henneman, R.C. Hennekam, A. Ciolfi, S. Pizzi, M. Tartaglia, P.M. Campeau, J. Rousseau, M.A. Levy, L. Brick, M. Kozenko, T.B. Balci, V.M. Siu, A. Stuart, M. Kadour, J. Masters, K. Takano, T. Kleefstra, N. de Leeuw, M. Field, M. Shaw, J. Gecz, G. Merla, P.J. Ainsworth, H. Lin, D.I. Rodenhiser, M.J. Friez, M. Tedder, J.A. Lee, B.R. DuPont, R.E. Stevenson, S.A. Skinner, C.E. Schwartz, D. Genevieve, Bekim Sadikovic;
London, Canada

PL2.2 Identity-by-descent detection across 487,409 British samples reveals fine-scale population structure, evolutionary history, and trait associations

Juba Nait Saada*, G. Kalantzis, D. Shyr, M. Robinson, A. Gusev, P. Palamara;
Oxford, United Kingdom

PL2.3 Large-scale targeted sequencing identifies risk genes for neurodevelopmental disorders

Malin Kvarnung, T. Wang, K. Hoekzema, D. Vecchio, H. Wu, A. Sulovari, B.P. Coe, M.A. Gillentine, A.B. Wilfert, A. Lindstrand, A. Nordgren, B. Anderlid, J.A. Rosenfeld, P. Liu, -. ASID Consortium, I.E. Scheffer, N. Brunetti-Perri, N. Rommelse, D.G. Amaral, G.W.E. Santen, E. Trabetti, Z. Sedláček, J.J. Michaelson, E. Courchesne, F.R. Kooy, -. The SPARK Consortium, C. Romano, H. Peeters, R.A. Bernier, J. Gecz, K. Xia, E.E. Eichler, M. Nordenskjöld;
Stockholm, Sweden

PL2.4 Genomic and transcriptomic profiling of malformations of cortical development: from tissue to single-cell resolution

Sara Baldassari*, M. Chipaux, E. Marsan, S. Ferrand‑Sorbets, G. Dorfmüller, H. Adle‑Biassette, S. Baulac;
Paris, France

PL2.5 TAD-shuffling at the FGF8 locus causes Split-Hand/Foot Malformation type 3

Giulia Cova*, R. Schöpflin, R. Falcone, B. Timmermann, L. Wittler, O. Zuffardi, M. Spielmann, S. Mundlos;
Berlin, Germany

PL2.6 The enrichment of breakpoints in late-replicating chromatin provides novel insights into chromoanagenesis mechanisms

Nicolas Chatron*, G. Giannuzzi, P. Rollat-Farnier, F. Diguet, E. Porcu, T. Yammine, K. UGUEN, Z. Bellil, J. Lauer Zillhardt, A. Sorlin, F. Ader, A. Afenjar, J. Andrieux, C. Bardel, E. Calpena, S. Chantot-Bastaraud, P. Callier, N. Chelloug, E. Chopin, M. Cordier, C. Dubourg, L. Faivre, F. Girard, S. Heide, Y. Herenger, S. Jaillard, B. Keren, S.J.L. Knight, J. Lespinasse, L. Lohmann, N. Marle, R. Maroofian, A. Masurel-Paulet, M. Mathieu-Dramard, C. Metay, A.T. Pagnamenta, M. Portnoï, F. Prieur, M. Rio, J. Siffroi, S. Valence, J.C. Taylor, A.O.M. Wilkie, P. Edery, A. Reymond, D. Sanlaville, C. Schluth-Bolard;
Lyon, France

Chairs:  Celine Lewis & Sam Riedijk
Virtual Session Room 5

PL3.1  ELPAG Award Lecture

Heather Skirton;
United Kingdom

Chairs:  Maurizio Genuardi & Joris Veltman
Virtual Session Room 1

PL4.1  Mendel Lecture

Aviv Regev;
Cambridge, United States

Chairs:  Maurizio Genuardi & Joris Veltman
Virtual Session Room 1

PL5.1  ESHG Award Lecture

Wendy Bickmore;
Edinburgh, United Kingdom

Chairs:  Maurizio Genuardi & Joris Veltman
Virtual Session Room 1

EJHG-SN Citation Awards

ESHG Awards for Best Presentations by Young Investigators

European DNA Day Contest

Closing Address

Concurrent Sessions

Chairs:   Maris Laan & Michael Speicher
Virtual Session Room 1

C01.1 Consistency of carrier screening guidelines across seven populations and 408,00 individuals

Aishwarya Arjunan, R. Ben-Shachar, R. Torres, K. Johansen Taber, K.E. Kaseniit, D. Muzzey;
South San Francisco, United States

C01.2 Expanded carrier screening of recessive disorders (CarrierTest) in clinical practice

Jan Diblík, M. Bittóová, F. Lhota, F. Zembol, L. Dohnalová, Z. Vilímová, I. Soldátová, M. Hrabíková, I. Pavlechová, M. Koudová, D. Stejskal;
Praha, Czech Republic

C01.3 Exome sequencing reveals variants in known and novel candidate genes for severe sperm motility disorders

Manon S. Oud, B.J. Houston, L. Volozonoka, F.K. Mastrorosa, B. Alobaidi, P.F. de Vries, G. Astuti, L. Ramos, R. Burke, R.I. McLachlan, M.K. O’Bryan, J.A. Veltman, H.E. Chemes, H. Sheth;
Nijmegen, Netherlands

C01.4 Identification of novel causes for male infertility: loss-of-function variants in MSH4 and MSH5

Margot J. Wyrwoll*, C. Friedrich, E. Kaminsky, C. Krallmann, S. Kliesch, F. Tüttelmann;
Münster, Germany

C01.5 Non-invasive prenatal diagnosis by genome-wide haplotyping of cell-free plasma DNA

Huiwen Che*, D. Villela, E. Dimitriadou, C. Melotte, N. Brison, M. Neofytou, K. Van Den Bogaert, O. Tsuiko, K. Devriendt, E. Legius, M. Zamani Esteki, T. Voet, J.R. Vermeesch;
Leuven, Belgium

C01.6 Trio exome/whole exome sequencing in prenatal diagnosis: Experiences from >400 cases shows a high diagnostic yield and a great benefit for pregnancy management and genetic counselling.

Heinz Gabriel, C. Wilhelm, F. Battke, E. Goldmann, C. Bus, S. Biskup;
Tuebingen, Germany

Chairs:  Yasemin Alanay & Enza Maria Valente
Virtual Session Room 2

C02.1 SCAF4 loss of function in humans and Drosophila implicates mRNA transcriptional termination in neurodevelopmental disorders

A. Fliedner, P. Kirchner, K.E. Agre, I. de Graaf-van de Laar, M. Dutra Clarke, L. Davis-Keppen, A.B. Ekici, A. Gregor, N. Lippa, K. McWalter, G. Mirzaa, G. Noh, L. Ohden, D.A. Scott, S. Lalani, R. Straussberg, R. Cohen, A. Wiesener, Christiane Zweier;
Erlangen, Germany

C02.2 Mutation-specific pathophysiological mechanisms in a new SATB1-associated neurodevelopmental disorder

Joery den Hoed*, E. de Boer, N. Voisin, N. Guex, L. Snijders Blok, J. Chrast, The DDD study, L. Manwaring, M. Willing, A. Waheeb, M. Osmond, K. McWalter, A. Vitobello, F. Demurger, A. Lavillaureix, S. Odent, B. Mazel, L. Faivre, I. Thiffault, C. Schwager, S.M. Amudhavalli, J.A. Rosenfeld, K. Radtke, E. Preiksaitiene, E. Ranza, C. Depienne, A. Kuechler, S. Mohammed, Y. Hamzavi Abedi, V.R. Bonagura, B. Zuccarelli, B. Horist, V. Krishnamurthy, A.A. Kattentidt-Mouravieva, L. Granger, A. Petersen, K.L. Jones, M. Sinnema, A.P.A. Stegmann, R. Newbury-Ecob, U. Kini, D.F. Newbury, C. Gilissen, H. Brunner, T. Kleefstra, A. Reymond, L.E.L.M. Vissers, S.E. Fisher;
Nijmegen, Netherlands

C02.3 De novo frameshift variants in the neuronal splicing factor NOVA2 result in a common C-terminal part and cause a severe form of neurodevelopmental disorder

Francesca Mattioli*, G. Hayot, N. Drouot, B. Isidor, J. Courraud, M. Hinckelmann, F. Tran Mau-Them, C. Sellier, A. Goldman, A. Telegrafi, A. Boughton, C. Gamble, S. Moutton, A. Quartier, N. Jean, P. Van Ness, S. Grotto, S. Nambot, G. Douglas, Y. Si, J. Chelly, Z. Shad, E. Kaplan, R. Dineen, C. Golzio, N. Charlet, J. Mandel, A. Piton;
Illkirch, France

C02.4 Location, location, location: protein truncating variants in different loci of SRCAP cause three distinct neurodevelopmental disorders, associated with distinctive DNA methylation signatures

Dmitrijs Rots*, E. Chater-Diehl, A.J.M. Dingemans, M. Siu, C. Cytrynbaum, N. Hoang, S. Walker, S. Scherer, R. Pfundt, T. Rinne, T. Gardeitchik, B.B.A. de Vries, C.T.R.M. Stumpel, S.J.C. Stevens, J. van Harssel, D.G.M. Bosch, K.L.I. van Gassen, E. van Binsbergen, C.M. de Geus, M. Hempel, D. Lessel, J. Denecke, A. Slavotinek, J. Strober, L.B. Ousager, M. Larsen, L. Schultz-Rogers, E. Morava, E.W. Klee, I.R. Berry, J. Campbell, K. Lindstrom, A.M. Neumeyer, J.A. Radley, C. Phornphutkul, W.G. Wilson, B. Schmidt, S. Meyn, K. Ounap, K. Reinson, S. Pajusalu, C. Ruivenkamp, A. van Haeringen, R. Cuperus, GeneDx inc., L.E.L.M. Vissers, H.G. Brunner, T. Kleefstra, D.A. Koolen, R. Weksberg;
Nijmegen, Netherlands

C02.5 Mechanistic dissection of chromatin topology disruption in the 5q14.3 MEF2C locus as an indirect driver of neurodevelopmental disorders

K. Mohajeri, Eva D’haene*, R. Yadav, H. Gu, B. Menten, A. Presser Aiden, C. Lowther, S. Erdin, E. Lieberman Aiden, J. Gusella, S. Vergult, M. Talkowski;
Gent, Belgium

C02.6 Crispr-Cas9-engineered Pigv341E mouse model mirrors the human phenotype, reveals a hippocampal synaptic defect and suggests a major role of impaired Abl1/Ephrin signaling pathway in GPI anchor deficiency

Miguel Rodríguez de los Santos, M. Rivalan, F.S. David, A. Knaus, A. Stumpf, L. Moreno Velasquez, A. Voigt, D. Mattei, M. Long, L. Wittler, B. Timmermann, D. Horn, S. Mundlos, U. Kornak, D. Schmitz, Y. Winter, P.M. Krawitz;
Berlin, Germany

Chairs:  Christian Gilissen & Zoltan Kutalik
Virtual Session Room 3

C03.1 Reconciling GWAS and Mendelian genetics through core-gene identification

Olivier B. Bakker, A. Claringbould, H. Westra, S. Mulcahy Symmons, M. Swertz, I.H. Jonkers, L. Franke, P. Deelen;
Groningen, Netherlands

C03.2 Improved de novo mutation detection through deep learning

Karolis Šablauskas*, W. Steyaert, D. Rots, R. Pfundt, H.G. Yntema, H.G. Brunner, A. Hoischen, L.E.L.M. Vissers, C. Gilissen;
Nijmegen, Netherlands

C03.3 GestaltMatch: breaking the limits of rare Mendelian disorder diagnosis by matching patients with next-generation phenotyping

Tzung-Chien Hsieh*, A. Bar-Haim, G. Nadav, T.J. Pantel, N. Fleischer, P. Krawitz;
Bonn, Germany

C03.4 Untranslated region (UTR) variant analysis across 71,702 genomes to build a framework for variant interpretation

Sander Pajusalu*, N.J. Lake, M. Lek;
New Haven, United States

C03.5 Hotspot detection in homologous protein domains using de novo mutations from 31,058 patients identify candidate developmental disorder genes

Laurens van de Wiel*, H. Venselaar, L.E.L.M. Vissers, G. Vriend, J.A. Veltman, C. Gilissen;
Nijmegen, Netherlands

C03.6 Cell type specific genetic regulation of gene expression across human tissues

Sarah Kim-Hellmuth, F. Aguet, M. Oliva, S. Kasela, M. Muñoz-Aguirre, V. Wucher, GTEx Consortium, R. Guigó, B.E. Stranger, K.G. Ardlie, T. Lappalainen;
Munich, Germany

Chairs:  Carla Oliveira & Conxi Lazaro
Virtual Session Room 1

C04.1 Unique somatic mutation lanscape enhances tumor predisposition in the kidney proximal tubule

Irene Franco, H.T. Helgadottir, A. Moggio, M. Larsson, P. Vrtacnik, A. Johansson, N. Norgren, P. Lundin, D. Mas-Ponte, J. Nordström, T. Lundgren, P. Stenvinkel, L. Wennberg, F. Supek, M. Eriksson;

C04.2 TFEB constitutive activation underlies polycystic kidney and renal carcinoma in Birt-Hogg-Dube’ syndrome

Chiara Di Malta, G. Napolitano, A. Esposito, M. Matarese, V. Benedetti, A. Zampelli, D. Siciliano, A. Venuta, M. Cesana, C. Vilardo, E. Nusco, J. Monfregola, A. Ballabio;
Pozzuoli (NA), Italy

C04.3 Oncogenic transcription factors are over-represented in mutated active DNA binding sites in neuroblastoma and Wilms tumor

Vito A. Lasorsa*, F. Cimmino, M. Avitabile, S. Cantalupo, A. Montella, B. De Angelis, M. Morini, C. de Torres, A. Castellano, F. Locatelli, A. Iolascon, M. Capasso;
Napoli, Italy

C04.4 Characterization of circRNA profiles in childhood acute lymphoblastic leukemia

Angela Gutierrez-Camino*, M. Caron, C. Richer, E. Lopez-Lopez, I. Martin-Guerrero, B. Frutos, P. St-Onge, A. Bataille, D. Sinnett;
Leioa, Spain

C04.5 Patient-derived PDAC organoids recapitulate tumor cell state heterogeneity and functional hierarchy in vitro

Teresa G. Krieger*, J. Jabs, S. LeBlanc, A. Giri, O. Strobel, R. Eils, C. Conrad;
Berlin, Germany

C04.6 Integrative analyses of 100 genomes of Basal Cell Carcinoma in the context of transcription and methylation profiles

Sergey I. Nikolaev, A. Yurchenko, A. Sartori, I. Padioleau, F. Rajabi, L. Parmentier, D. Salomon, E. Dermitzakis, H. Ongen;

Chairs:  Valerie Cormier-Daire & Aurora Pujol
Virtual Session Room 2

C05.1 Investigating the role of KMT2C in heart development

Shona C. Borland, G. Tenin, R. Monaghan, S. Williams, M. Zi, C. Wilson, S. Prehar, E. Cartwright, S. Abraham, B. Keavney;
Manchester, United Kingdom

C05.2 Mutations in KDR, encoding for vascular endothelial growth factor receptor 2, contribute to Tetralogy of Fallot

Doris Skoric-Milosavljevic*, N. Lahrouchi, F. Bosada, G. Dombrowsky, F. Tjong, I. El Bouchikhi, M. Hababa, S. Williams, R. Walsh, L. Beekman, A. Ilgun, R. Lesurf, E. Audain, J. Breckpot, B.J. Mulder, S. Clur, S. Mital, B. Keavney, M. Hitz, V. Christoffels, E.M. Lodder, A.V. Postma, C.R. Bezzina;
Amsterdam, Netherlands

C05.3 Bi-allelic loss-of-function mutations in PLD1 cause congenital right-sided cardiac valve defects and neonatal cardiomyopathy

Najim Lahrouchi*, A. Postma, C.M. Salazar, D. De Laughter, F. Tjong, L. Piherová, F.Z. Bowling, D. Zimmerman, E.M. Lodder, A. Ta-Shma, Z. Perles, L. Beekman, A. Ilgun, Q. Gunst, M. Hababa, D. Škorić‐Milosavljević, P. de Knijff, R. de Leeuw, J.Y. Robinson, S.C. Burn, H. Mustafa, M. Ambrose, T. Moss, J. Jacober, D.M. Niyazov, A. Rousounides, A. Aristidou-Kallika, G. Tanteles, M. Magliozzi, F.C. Radio, G.W.E. van Santen, J.C. Herkert, O. Elpeleg, M. van den Hoff, B. Mulder, M.V. Airola, S. Kmoch, J.V. Barnett, S. Clur, M.A. Frohman, C.R. Bezzina;
Amsterdam, Netherlands

C05.4 Pathogenic variants in THSD4, encoding the ADAMTS-Like 6 protein, predispose to inherited thoracic aortic aneurysm

Sandy Elbitar*, M. Renard, P. Arnaud, N. Hanna, M. Jacob, D. Guo, K. Tsutsui, M. Gross, K. Kessler, L. Tosolini, V. Dattilo, S. Dupont, J. Jonquet, M. Langeois, L. Benarroch, M. Aubart, Y. Ghaleb, Y. Abou Khalil, M. Varret, P. El Khoury, B. Ho-Tin-Noé, Y. Alembik, S. Gaertner, B. Isidor, L. Gouya, O. Milleron, K. Sekiguchi, D. Milewicz, J. De Backer, C. Le Goff, J. Michel, G. Jondeau, L.Y. Sakai, C. Boileau, M. Abifadel;
Paris, France

C05.5 Functional characterization of rare SHOX2 variants identified in sinus node dysfunction and atrial fibrillation

Sandra Hoffmann, C. Paone, S.A. Sumer, S. Diebold, B. Weiss, R. Roeth, S. Clauss, I. Klier, S. Kääb, A. Schulz, P.S. Wild, A. Ghrib, T. Zeller, R.B. Schnabel, S. Just, G.A. Rappold;
Heidelberg, Germany

C05.6 A novel microRNA in human induced pluripotent stem cell-derived cardiomyocytes regulates hypertrophy and is a biomarker of left ventricular hypertrophy

A. Turner, P. Aggarwal, A. Matter, C. Gu, D.K. Arnett, Ulrich Broeckel;
Milwaukee, United States

Chairs:  Elfride de Baere & Nicola Brunetti-Pierri
Virtual Session Room 3

C06.2 Whole Exome Sequencing, Molecular Assays, Immunohistology and Animal Models associate USP48 to Hereditary Hearing Loss

Sissy Bassani*, A. Morgan, M. Cocca, N. Voisin, J. Chrast, S. Pradervand, N. Guex, B. Delprat, M. Rossel, H. Locher, E. Van Beelen, M. Tangui, P. Gasparini, G. Girotto, A. Reymond;
Trieste, Italy

C06.3 Ablation of the congenital microcoria (MCOR) critical region on 13q32.1 activates common-type glaucoma signaling pathways challenging a developmental etiology of MCOR-associated glaucoma.

Clementine Angee*, B. Nedelec, P. David, S. Gerber, S. Crippa, B. Passet, J. Vilotte, N. Chassaing, J. Kaplan, C. Costic, P. Calvas, J. Rozet, L. Fares-Taie;
Paris, France

C06.4 Mouse and human studies support a role for CAPN15 variants in cataract and microphthalmia

C. Zha, C.A. Farah, Richard J. Holt, F. Ceroni, L. AlAbdi, A.O. Khan, R. Helaby, F.S. Alkuray, A. Kraus, N.K. Ragge, W.S. Sossin;
Oxford, United Kingdom

C06.5 DYNC2H1 hypomorphic or retina-predominant variants cause non-syndromic retinal degeneration

Anjali V. Vig, J.A. Poulter, D. Ottaviani, E. Tavares, K. Toropova, A.M. Tracewska, A. Mollica, J. Kang, O. Kehelwathugoda, T. Paton, J.T. Maynes, G. Wheway, G. Arno, K.N. Khan, M. McKibbin, C. Toomes, M. Ali, M. Di Scipio, S. Li, J. Ellingford, G. Black, A. Webster, M. Rydzanicz, P. Stawiński, R. Płoski, A. Vincent, M.E. Cheetham, C.F. Inglehearn, A. Roberts, E. Heon;
Toronto, Canada

C06.6 Proteasome subunit PSMC3 variants cause neurosensory syndrome combining deafness and cataract due to proteotoxic stress

A. Kröll-Hermi, F. Ebstein, C. Stoetzel, V. Geoffroy, E. Schaefer, S. Scheidecker, S. Bär, M. Takamiya, K. Kawakami, B. Zieba, F. Studer, V. Pelletier, C. Speeg-Schatz, V. Laugel, D. Lipsker, F. Sandron, S. McGinn, A. Boland, J. Deleuze, L. Kuhn, J. Chicher, P. Hammann, S. Friant, C. Etard, E. Krüger, Jean Muller, U. Strähle, H. Dollfus;
Strasbourg, France

Chairs:  Celine Lewis & Ramona Moldovan
Virtual Session Room 4

C07.1 Implementing a hybrid clinical/research model in genomic medicine: post 100,000 Genomes Project

Christine Patch, E. Thomas, F. Maleady Crowe, R. Wier, T. Fowler, M. Bishop, A. Pichini;
London, United Kingdom

C07.2 A tailored approach towards informing relatives at risk of inherited cardiac diseases: preliminary results of a randomized controlled trial

Lieke M. Van den Heuvel*, Y.M. Hoedemaekers, A.F. Baas, M.J.H. Baars, E.M.A. Smets, J.P. van Tintelen, I. Christiaans;
Amsterdam, Netherlands

C07.3 Measuring the burden of direct-to-consumer genetic testing on clinical genetics services

Jane M. Tiller*, M. Millward, M. Bogwitz, H. Kincaid, S. Taylor, A. Trainer, P. Lacaze;
Melbourne, Australia

C07.4 Critical components of informed consent for genetic testing: Results of a Delphi Consensus process

Kelly E. Ormond, M. Borensztein, A.H. Buchanan, W. Faucett, M.L.G. Hallquist, H.L. Peay, M.E. Smith, E. Tricou, W.R. Uhlmann, K.E. Wain, C.R. Coughlin II;
Stanford, United States

C07.5 Public attitudes towards human germline gene editing: a baseline survey in the Netherlands

Diewertje Houtman*, M. Polak, B. Vijlbrief, P. Verheggen, R. Hofstra, S. Riedijk;
Rotterdam, Netherlands

C07.6 Does Genetic Counseling lead to effective coping with genetic risk information?

Barbara B. Biesecker, M.T. Cho;
Bethesda, United States

Chairs:   Christian Gilissen & Francesca Forzano
Virtual Session Room 1

C08.1 Project Baby Bear: The first state-funded quality improvement project of rapid Whole Genome Sequencing in neonatal and pediatric intensive care units in the USA

Katarzyna A. Ellsworth, S. Caylor, W. Benson, C. Ashburner, J. Carmichael, E. Cham, S. Chowdhury, J. Cleary, A. D’Harlingue, L. Farnaes, J. Hunt, C. Hobbs, K. Houtchens, P. Joe, J. Knight, A. Kochhar, M. Joseph, J. Limon, M. Martin, S. Nahas, K.A. Rauen, A. Schwarz, S.P. Shankar, R. Spicer, M. Rojas, O. Vargas-Shiraishi, K. Wigby, N. Zadeh, S. Kingsmore, D. Dimmock;
San Diego, United States

C08.2 Integration of genome sequencing into health care – experiences from 3211 rare disease patients show high diagnostic rates across multiple clinical entities

Anna Lindstrand, H. Stranneheim, K. Lagerstedt-Robinson, M. Kvarnung, N. Lesko, D. Nilsson, B. Anderlid, H. Arnell, C. Backman Johansson, M. Barbaro, E. Björck, H. Bruhn, J. Eisfeldt, M. Engvall, C. Freyer, G. Grigelioniene, P. Gustavsson, A. Hammarsjö, M. Hellström-Pigg, A. Jemt, M. Laaksonen, S. Lind Enoksson, M. Magnusson, H. Malmgren, K. Naess, M. Nordenskjöld, M. Oscarson, M. Pettersson, C. Rasi, A. Rosenbaum, E. Sahlin, T. Stödberg, B. Tesi, E. Tham, H. Thonberg, U. von Döbeln, S. Vonlanthen, A. Wikström, J. Wincent, O. Winqvist, A. Wredenberg, S. Ygberg, R.H. Zetterström, P. Marits, M. Johansson-Soller, M. Johansson Soller, A. Nordgren, V. Wirta, A. Wedell;
Stockholm, Sweden

C08.3 Genomic loci susceptible to systematic sequencing bias in clinical whole genomes

Timothy M. Freeman*, Genomics England Research Consortium, D. Wang, J. Harris;
Sheffield, United Kingdom


Systematic analysis of short tandem repeats in 38,256 exomes provides additional diagnostic yield

Bart P.G.H. van der Sanden*, M. de Groot, J. Corominas, M. Pennings, R.P.P. Meijer, L.E.L.M. Vissers, E. Kamsteeg, C. Gilissen;
Nijmegen, Netherlands

C08.5 A cost-effectiveness and utility analysis of genomic sequencing in a prospective versus historical cohort of complex pediatric patients

Alison Yeung, N.B. Tan, T.Y. Tan, Z. Stark, N. Brown, M.J. Hunter, M. Delatycki, C. Stutterd, R. Savarirayan, G. McGillivray, R. Stapleton, S. Kumble, L. Downie, M. Regan, S. Lunke, B. Chong, D. Phelan, G. Brett, A. Jarmolowicz, Y. Prawer, G. Valente, Y. Samarinsky, M. Martin, C. McEwan, I. Goranitis, C. Gaff, S.M. White;
Parkville, Australia

C08.6 The impact of the 100,000 Genomes Project on rare disease in national healthcare

Damian Smedley, S. Abbs, G. Arno, E. Baple, M. Barnes, P. Beales, M. Bitner-Glindzicz, G. Black, P. Brennan, G. Chan, P. Chinnery, V. Cipriani, S. Ellard, J. Ellingford, P. Elliott, H. Firth, F. Flintner, K. Ibanez Garikano, H. Houlden, M. Irving, J. Jacobsen, E. McDonagh, D. McMullan, L. Moutsianas, W. Newman, W.H. Ouwehand, T. Ratnaike, A. Rueda Martin, C. Penkett, F. Raymond, J. Sayer, R. Scott, K. Smith, H. Stark, K. Stirrups, J. Taylor, E. Thomas, A. Tucci, J. Vandrovcova, L. Vestito, A. Webster, W. Wei, M. Wielscher, H. Williams, A. Wilkie, C. Wright, A. Rendon, M. Caulfield, ,. NIHR BioResource, ,. Genomics England Research Consortium;
London, United Kingdom

Chairs:  Zeynep Tümer & Johannes Zschocke
Virtual Session Room 2

C09.1 The Australian Genomic Health Alliance Mitochondrial Flagship – A national approach to genomic diagnostics

David Thorburn, N. Baker, S. Balasubramaniam, D. Bratkovic, D. Coman, A. Compton, M. Delatycki, C. Ellaway, M. Fahey, J. Fletcher, A. Frazier, R. Ghaoui, H. Goel, D. Hock, M. Kava, N. Lake, P. Lamont, J. Lee, J. Panetta, L. Phillips, R. Rius, M. Ryan, N. Smith, D. Stroud, M. Tchan, M. Walsh, M. Wallis, A. Welch, C. Wools, J. Christodoulou;
Melbourne, Australia

C09.2 High resolution respirometric analysis of a Barth Syndrome disease model

Gregor Oemer*, K. Lackner, J. Koch, E.R. Werner, C. Doerrier, G. Krumschnabel, G. Leman, S. Dubrac, R. Houtkooper, J. Zschocke, M.A. Keller;
Innsbruck, Austria

C09.3 Recurrent de novo ATAD3 duplications cause fatal perinatal mitochondrial cardiomyopathy, persistent hyperlactacidemia, encephalopathy and heart-specific mitochondrial oxidative phosphorylation complex I deficiency.

A.E. Frazier, Alison G. Compton, Y. Kishita, D.H. Hock, A.E. Welch, S.S.C. Amarasekera, R. Rius, L.E. Formosa, A. Imai-Okazaki, D. Francis, M. Wang, N.J. Lake, S. Tregoning, J.S. Jabbari, A. Lucattini, K.R. Nitta, A. Ohtake, K. Murayama, D.J. Amor, G. McGillivray, F.Y. Wong, M.S. van der Knaap, R.J. Vermeulen, E.J. Wiltshire, J.M. Fletcher, B. Lewis, G. Baynam, C. Ellaway, S. Balasubramaniam, K. Bhattacharya, M.L. Freckmann, R.J. Taft, S. Sadedin, M.J. Cowley, A.E. Minoche, S.E. Calvo, V.K. Mootha, M.T. Ryan, Y. Okazaki, D.A. Stroud, C. Simons, J. Christodoulou, D.R. Thorburn;
Melbourne, Australia

C09.4 Hyperuricemia and gout caused by missense mutation in D-lactate dehydrogenase, revealing novel enzymatic activity

Max Drabkin*, Y. Yogev, L. Zeller, R. Zarivach, R. Zalk, D. Halperin, O. Wormser, E. Gurevich, D. Landau, R. Kadir, Y. Perez, O.S. Birk;
Beer-Sheva, Israel

C09.5 Metabolite set enrichment improves biomarker identification and detection in untargeted metabolic profiling (UMP) data for patients with inborn errors of metabolism

Brechtje Hoegen*, U.F.H. Engelke, K.L.M. Coene, J.E. Hampstead, P. Kulkarni, R.A. Wevers, H.G. Brunner, C. Gilissen;
Nijmegen, Netherlands

C09.6 A genome-wide association study for a proxy non-alcoholic fatty liver phenotype identifies novel loci and trait-relevant candidate genes

M. Vujkovic, S. Ramdas, K. Gawronski, K. Lorenz, M. Serper, D.E. Kaplan, R. Carr, K.M. Lee, S. Saiju Pyarajan, T. Edwards, D. Klarin, Y.V. Sun, D.R. Miller, P.D. Reaven, L.S. Phillips, C.J. O’Donnell, J.B. Meigs, P.W.F. Wilson, R. Vickers-Smith, H.R. Kranzler, A.C. Justice, M. Gaziano, S. Muralidhar, S.L. DuVall, T.L. Assimes, J.S. Lee, P.S. Tsao, D.J. Rader, C.D. Brown, S.M. Damrauer, J.A. Lynch, D. Saleheen, Benjamin F. Voight, K.M. Chang, on behalf of the VA Million Veteran Program;
Philadelphia, United States

Chairs:  Joris Veltman & Martin Kircher
Virtual Session Room 3

C10.1 Recessive vs dominant GWAS of 82,516 coding variants on electronic health records in a population-wide analysis of 176,899 Finns

Henrike O. Heyne, J. Karjalainen, S.M. Lemmelä, FinnGen, A.S. Havulinna, M. Kurki, A. Palotie, M.J. Daly;
Helsinki, Finland

C10.2 Germline genetic testing following tumor sequencing in cancer patients has a remarkably high yield of clinically important findings that inform patient care

Stephen Lincoln, K. Das, N. Ngo, S. Michalski, S. Yang, D. Pineda, E. Esplin, S. Aradaya, R. Nussbaum;
San Francisco, United States

C10.3 The first genotype-phenotype study on European carriers of CDH1 germline mutations

José García-Peláez*, R. Monteiro, L. Sousa, H. Pinheiro, S. Castedo, L. Garrido, M. Teixeira, G. Michils, V. Bours, R. de Putter, L. Golmard & M. Blanluet, C. Colas, P. Benusiglio, S. Aretz & I. Spier, R. Hüneburg, L. Gieldon, E. Schröck, E. Holinski-Feder & V. Steinke, D. Calistri & G. Tedaldi, G. Ranzani, M. Genuardi, C. Silveira & I. Silva, M. Krajc & A. Blatnik, S. Novakovic, A. Patiño-García, J. Soto, C. Lázaro, G. Capellá, J. Brunet-Vidal, J. Balmaña, E. Domínguez-Garrido, M. Ligtenberg, E. Fewings, R. Fitzgerald, E. Woodward, G. Evans, H. Hanson, K. Lagerstedt-Robinson, S. Bajalica-Lagercrantz, C. Egas, C. Martínez-Bouzas et al., K. Dahan & D. Feret, N. Hoogerbrugge, M. Tischkowitz, C. Oliveira;
Porto, Portugal

C10.4 Enhancing rare variant interpretation in inherited arrhythmias through quantitative analysis of 5182 cases from long QT syndrome and Brugada syndrome consortia cohorts and gnomAD population controls

Roddy Walsh, N. Lahrouchi, C. Glinge, C. Krijger, D. Skoric-Milosavljevic, N. Whiffin, F. Mazzarotto, J.S. Ware, R. Tadros, International Brugada Syndrome Genetics Consortium, International LQTS Genetics Consortium, C.R. Bezzina;
Amsterdam, Netherlands

C10.5 Genome wide association study based on cardiac magnetic resonance imaging in 23,634 individuals identifies five new loci associated with left atrial enlargement

Gustav Ahlberg*, L. Andreasen, J. Ghouse, S. Haunsoe, J.H. Svendsen, M.S. Olesen;
Copenhagen, Denmark

C10.6 Genetic interactions modulate lipid plasma levels and cellular uptake

Magdalena Zimon, Y. Huang, A. Trasta, J. Liu, C. Chen, A. Halavatyi, P. Blattmann, B. Klaus, C. Whelan, D. Sexton, S. John, E. Tsai, W. Huber, R. Pepperkok, H. Runz;
Heidelberg, Germany

Chairs:  Valerie Cormier-Daire & Aurora Pujol
Virtual Session Room 4

C11.1 Biallelic variants in KYNU cause a multisystemic syndrome with hand hyperphalangism

Nadja Ehmke, K. Cusmano-Ozog, R. Koenig, M. Holtgrewe, B. Nur, E. Mihci, H. Babcock, C. Gonzaga-Jauregui, J.D. Overton, J. Xiao, B. Fischer-Zirnsak, C. Huber, U. Kornak, S.H. Elsea, V. Cormier-Daire, C.R. Ferreira;
Berlin, Germany

C11.2 Integrated genome and transcriptome analyses solves about one third of the patients with rare developmental disorders and negative first-line molecular investigations

Antonio Vitobello, F. Tran Mau-Them, A.L. Bruel, Y. Duffourd, E. Tisserant, P. Callier, S. Moutton, S. Nambot, D. Lehalle, N. Jean-Marçais, J. Delanne, C. Racine, J. Thevenon, C. Poe, T. Jouan, M. Chevarin, M. Willems, C. Coubes, D. Geneviève, N. Houcinat, A. Masurel-Paulet, A. Mosca-Boidron, A. Sorlin, B. Isidor, S. Heide, A. Afenjar, D. Rodriguez, C. Mignot, D. Heron, M. Vincent, P. Charles, S. Odent, C. Dubourg, A. Faudet, B. Keren, B. Cogné, A. Boland, R. Olaso, C. Philippe, J.F. Deleuze, L. Faivre, C. Thauvin-Robinet;
Dijon, France

C11.3 Characterization and treatment of overactive KATP channels associated with Cantú syndrome in zebrafish

Helen I. Roessler*, S.S. Singareddy, C. McClenaghan, S. Savelberg, F. Tessadori, J. Bakkers, R. Tyron, C.G. Nichols, G. van Haaften;
Utrecht, Netherlands

C11.4 Biallelic MADD variants cause a phenotypic spectrum ranging from developmental delay to a multisystem disorder

Pauline E. Schneeberger*, F. Kortüm, G.C. Korenke, M. Alawi, R. Santer, M. Woidy, D. Buhas, S. Fox, D. McKnight, M. Alfadhel, B.D. Webb, E.G. Coci, R. Abou Jamra, A. Finck, M. Siekmeyer, S. Biskup, C. Heller, E.M. Maier, P. Javaher-Haghighi, M.F. Bedeschi, P.F. Ajmone, M. Iascone, H. Peeters, K. Ballon, J. Jaeken, A. Rodríguez Alonso, M. Palomares-Bralo, F. Santos-Simarro, M.E.C. Meuwissen, D. Beysen, R. Kooy, H. Houlden, D. Murphy, M. Doosti, E.G. Karimiani, M. Mojarrad, R. Maroofian, B.D. Gelb, I. Kurth, M. Hempel, K. Kutsche;
Hamburg, Germany

C11.5 Modelling the developmental spliceosomal craniofacial disorder Burn-McKeown Syndrome using induced pluripotent stem cells

K. A. Wood, C. Rowlands, H. Thomas, S. Woods, J. O’Flaherty, S. Kimber, W. Newman, R. O’Keefe;
Manchester, United Kingdom

C11.6 A novel Bannayan-Riley-Ruvalcaba (BRRS)/CLOVES syndrome model in Xenopus tropicalis, by CRISPR/Cas9

Dionysia Dimitrakopoulou, S. Demuynck, K. Vleminckx;
Ghent, Belgium

Chairs:  Malte Spielmann & Enza Maria Valente
Virtual Session Room 5

C12.1 Polygenic background of psychotic disorders and genetic determinants of disease severity

Ari V. Ahola-Olli, Z. Misiewicz, N. Mars, M. Lähteenvuo, B. Neale, T. Männynsalo, E. Isometsä, A. Wegelius, J. Hietala, W. Haaki, O. Kampman, J. Veijola, J. Tiihonen, T. Kieseppä, J. Suvisaari, S. Hyman, M. Daly, A. Palotie;
Cambridge, United States

C12.2 Autism-linked Cullin3 germline haploinsufficiency impacts cytoskeletal dynamics and cortical neurogenesis through RhoA signaling

M. Amar, A. Pramod, V. Munive Herrera, N. Yu, L.R. Qiu, P. Moran-Losada, P. Zhang, C.A. Trujillo, J. Ellegood, J. Urresti, K. Chau, J. Diedrich, J. Chen, J. Gutierrez, J. Sebat, D. Ramanathan, J.P. Lerch, J.R. Yates III, A.R. Muotri, Lilia M. Iakoucheva;
La Jolla, United States

C12.3 Tissue-specific transcriptional and functional signatures in reciprocal genomic disorders : Insights from integrated mouse and human neuronal models

Rachita Yadav*, D. JC Tai, J. Wang, T. Aneichyk, S. Erdin, B. B Currall, K. O’Keefe, A. Stortchevoi, U. Rudolph, R. H. Perlis, J. F Gusella, M. E Talkowski;
Boston, United States

C12.4 Autism Comorbidities: Role of CHD8 during the Development of the Enteric Nervous System

Gaëlle L. Hayot*, C. Weber, C. Golzio;
Illkirch-Graffenstaden, France

C12.5 A human single-cell atlas of the Substantia nigra reveals novel cell-specific pathways associated with the genetic risk of Parkinson’s disease and neuropsychiatric disorders.

D. Agarwal, C. Sandor, V. Volpato, T. Caffrey, J. Monzon-Sandoval, R. Bowden, J. Alegre-Abarrategui, R. Wade-Martins, Caleb Webber;
Cardiff, United Kingdom

C12.6 Clinical and molecular complexity of X-linked clustering epilepsy, a disorder of cellular mosaics

Jozef Gecz, K. Kolc, L. Sadleir, C. Depienne, C. Marini, I.E. Scheffer, R.S. Moller, M. Trivisano, N. Specchio, R. Kumar, D. Pham, R. Roberts;
Adelaide, Australia

Chairs:  Michael Speicher & Malte Spielmann
Virtual Session Room 1

C13.1 Landscape of cohesin-mediated chromatin loops in the human genome

Fabian Grubert, R. Srivas, D. Spacek, M. Kasowski, M. Ruiz-Velasco, N. Sinnott-Armstrong, P. Greenside, A. Narasimha, Q. Liu, B. Geller, A. Sanghi, M. Kulik, S. Sa, M. Rabinovitch, A. Kundaje, S. Dalton, J. Zaugg, M. Snyder;
Stanford, United States

C13.2 Analysis of chromatin looping at joint endometrial-ovarian cancer risk loci to identify candidate target genes

Dylan Glubb, I. Jeong, A. Spurdle, T. O’Mara;
Brisbane, Australia

C13.3 When the silent genome gets loud: transcription of repeated genomic elements at the single-cell resolution in K27M-mutated high-grade gliomas

Marie Coutelier*, V. Lisi, S. Hébert, D. Faury, B. Krug, N. De Jay, N. Jabado, C.L. Kleinman;
Montreal, Canada

C13.4 CDH1 regulatory noncoding elements: a hidden master for tissue-specific E-cadherin expression

Celina São José*, A.R. Monteiro, A. Qamra, R. Acuna-Hidalgo, P. Tan, S. Mundlos, C. Oliveira;
Porto, Portugal

C13.5 Local gene co-expression: molecular characterisation, tissue specificity and its genetic control

Diogo Ribeiro*, A. Ramisch, E. Dermitzakis, O. Delaneau;
Lausanne, Switzerland

C13.6 Structural variants in HDAC9 that disrupt TWIST1 transcriptional regulation but not HDAC9 protein function are associated with craniofacial and limb malformations

Ramon Y. Birnbaum, N. Hirsch;
Beer-Sheva, Israel

Chairs:   Valerie Cormier-Daire & Elfride de Baere
Virtual Session Room 2

C14.1 Implication of FOXD2 in autosomal recessive syndromic CAKUT

Korbinian M. Riedhammer, M. Nguyen, B. Alhaddad, S.J. Arnold, G.J. Kim, U. Heemann, M. Schmidts, J. Hoefele;
Munich, Germany

C14.2 Heterozygous DACT1 mutations in patients with renal anomalies and features of Townes-Brocks syndrome

A. Christians, E. Kesdiren, I. Hennies, A.D. Hofmann, M. Trowe, F. Brand, Helge Martens*, I.A. Kindem, Z. Gucev, M. Zirngibl, R. Geffers, T. Seeman, A. Kispert, H. Billing, A. Bjerre, V. Tasic, D. Haffner, J. Dingemann, R.G. Weber;
Hannover, Germany

C14.3 Loss of UNC45A causes microvillus inclusion disease-like by impairing myosin-dependent epithelial morphogenesis

R. Duclaux-Loras, F. Charbit-Henrion, C. Lebreton, O. Nicolle, M. Rabant, C. Guerrera, A. Fabre, L. Faivre, G. Michaux, H. Uligh, F. Ruemmele, N. Cerf-Bensussan, Marianna Parlato;
Paris, France

C14.4 A comprehensive exome study of the genetic architecture of asthma reveals a putative novel patient subgroup defined by filaggrin truncating variants

Sophia R. Cameron-Christie*, H. Olsson, A. Mackay, Q. Wang, M. Hühn, D. Muthas, G. Lassi, J. Lindgren, G. Povysil, D.B. Goldstein, G. Belfield, I. Dillmann, Y. Ohne, S. Cohen, S. Young, A. Platt, S. Petrovski;
Cambridge, United Kingdom

C14.5 Random plasma glucose GWAS in 479,678 individuals: genetic relationships with impaired lung function and intestinal health

Marika A. Kaakinen, L. Jiang, A. Ulrich, L. Zudina, Z. Balkhiyarova, P. Todorov, T.H. Pers, V. Lagou, I. Prokopenko, MAGIC Investigators;
Guildford, United Kingdom

C14.6 A complementary study approach unravels novel players in the pathoetiology of Hirschsprung‘s disease

T. Mederer, Stefanie Schmitteckert, J. Volz, C. Martinez, R. Röth, T. Thumberger, V. Eckstein, J. Scheuerer, C. Thöni, F. Lasitschka, L. Carstensen, P. Günther, S. Holland-Cunz, R. Hofstra, E. Brosens, D. Schriemer, I. Ceccherini, M. Rusmini, J. Tilghman, B. Luzón-Toro, A. Torroglosa, S. Borrego, C. Szeman Tang, M. Garcia-Barcelo, P. Tam, N. Paramasivam, M. Bewerunge-Hudler, C. de la Torre, N. Gretz, G. Rappold, P. Romero, B. Niesler;
Heidelberg, Germany

Chairs:  Joris Veltman & Alexandre Reymond
Virtual Session Room 3


START: The STudy of Assisted Reproductive Technologies

Robert Lyle, C. Page, Y. Lee, K.L. Haftorn, A. Jugessur, J. Bohlin, H.K. Gjessing, H.K. Gjessing, P. Magnus, S. Håberg;
Oslo, Norway


Evaluating diagnostic challenges with ABCA4-related retinal disease – experience with a 7500 IRD patient cohort sent for genetic diagnostics

Johanna Känsäkoski, K. Kämpjärvi, S. Tuupanen, K. Wells, L. Sarantaus, P. von Nandelstadh, K. Merkkiniemi, H. Västinsalo, E. Mårtensson, R. Perez Carro, E. Sankila, J.W. Koskenvuo, S. Myllykangas, T. Alastalo;
Espoo, Finland


Insights into the retinal function of ciliopathy proteins gained through zebrafish models

M. Masek, Ruxandra Bachmann-Gagescu;
Zürich, Switzerland


Functional characterization of a Xenopus tropicalis knockout and a human cellular model of RCBTB1-associated inherited retinal disease shows involvement of RCBTB1 in the cellular response to oxidative stress

Marjolein Carron , T. Naert, G. Ascari, S. Demuynck, T. Van Nieuwenhuyzen, T. Rosseel, D. Priem, A. Kremer, H. Van Landeghem, S. Hoogstoel, F. Coppieters, C. Guérin, K. Vleminckx, E. De Baere;
Ghent, Belgium


Loss of function of RIMS2, a synaptic membrane exocytosis gene, causes a new phenotype characterized by congenital cone-rod synaptic disease associated with neurodevelopmental and pancreatic involvement

Sabrina Mechaussier , B. Almoallem, C. Zeitz, K. Van Schil, L. Jeddawi, J. Van Dorpe, C. Condroyer, O. Pelle, M. Polak, N. Boddaert, N. Bahi-Buisson, M. Cavallin, J. Bacquet, A. Mouallem-Bézière, O. Zambrowski, J. Sahel, I. Audo, J. Kaplan, J. Rozet, E. De Baere, I. Perrault;
Paris, France


Genetic and molecular analysis of urinary magnesium concentration in Scottish and Croatian populations

Christina B. Joseph, C.M. Stanton, C. Drake, T.S. Boutin, J.F. Wilson, O. Polasek, O. Devuyst, T. Hurd, C. Hayward;
Edinburgh, United Kingdom


Detection of deep intronic mutations by RNAseq in Alport syndrome

Paris, France


RNA-seq approach to detect splicing alterations in primary ciliary dyskinesia and non-CF bronchiectasis

Jelmer Legebeke, G. Wheway, H. Wai, W. Walker, J.S. Lucas, D. Baralle;
Southampton, United Kingdom


Combined exome/genome sequencing with in-house variant data repository mining confirm USP53 as a causal gene for intrahepatic cholestasis

Salem Alawbathani, M. Rocha, H. Arshad Cheema, R. Boustany, S. Nampoothiri, A. Alswaid, N. El Koofy, V. Karageorgou, I. Hövel, S. Khan, C. Beetz, A. Rolfs, P. Bauer, A.M. Bertoli-Avella, A.M. Bertoli-Avella;
Rostock, Germany


Elucidating the molecular mechanism underlying laterality defects

Dinu Antony, A. Maver, M.A. Deardorff, L. Slagter, K. Wu, Z. Bakey, E. Gulec, A. Gezdirici, H. Brunner, M. Schmidts;
Freiburg, Germany


Biallelic missense variant in SVBP causes impaired detyrosination of tubulin leading to complex hereditary spastic paraplegia without microcephaly

Edgard Verdura, N. Launay, G. Fernandez Garcia de Eulate, J. Ondaro, A. Schlüter, M. Ruiz, S. Fourcade, A. López de Munain, A. Pujol;
L’Hospitalet de Llobregat, Barcelona, Spain


Understanding the mechanism of RNF216-mediated neurodegeneration: genetic, proteomic, neuropathological and cellular approach

Sumedha Roy, P. Ervilha Pereira, N. Schuermans, A. Sieben, F. Thery, E. Mondragon Rezola, E. Debackere, P. LeBlanc, M. Galas, P. Santens, F. Impens, E. Bogaert, B. Dermaut;
Gent, Belgium


The genotype-phenotype correlation of intragenic RBFOX1 deletions.

Magdalena A. Paczkowska, M. Geremek, B. Nowakowska;
Warsaw, Poland


Mitochondrial dysfunction and oxidative stress contribute to the phenotype of FOXP1 deficiency

Jing Wang, H. Fröhlich, G.A. Rappold;
Heidelberg, Germany

Chairs:   Edward Dove & Ramona Moldovan
Virtual Session Room 4

C16.1 Regulating Preimplantation Genetic Diagnosis: A comparison of international policy trends and perspectives

Rosario Isasi, M.E. Ginoza;
Miami, United States

C16.2 Regulation of international direct-to-participant (DTP) genomic research: results and recommendations from a 31-country study

Ma’n Zawati, M. Rothstein, B. Knoppers;
Montreal, Canada

C16.3 Genomic sequencing capacity, data retention and personal access to raw data in Europe

Shaman Narayanasamy*, V. Markina, A. Thorogood, A. Blazkova, M. Shabani, B.M. Knoppers, B. Prainsack, R. Koesters;
Esch-sur-Alzette, Luxembourg

C16.4 The genome as individual property or common good. Conceptualization of the genome within a citizen forum

Chloé Mayeur, W. Van Hoof;
Anderlecht, Belgium

Chairs:  Nicola Brunetti Pierri & Zeynep Tümer
Virtual Session Room 1

C17.1 An innovative dual-reporter cell line to identify protein level modulators in drug-repositioning for rare genetic diseases: a proof-of-principle in Autosomal Dominant LeukoDystrophy (ADLD)

Elisa Giorgio, E. Pesce, E. Pozzi, E. Sondo, M. Lorenzati, M. Ferrero, G. Borrelli, E. Della Sala, A. Buffo, N. Pedemonte, A. Brusco;
Torino, Italy

C17.2 Low-dose infigratinib, an oral selective fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitor (TKI), demonstrates activity in preclinical models of achondroplasia (ACH)

Benoit Demuynck, J. Flipo, G. Li, C. Dambkowski, L. Legeai-Mallet;
Paris, France

C17.3 CRISPR/Cas9 gene editing approach completely repaired the causative COL4A5 10bp deletion in a naturally occurring dog model of Alport Syndrome.

Sergio Daga*, K. Capitani, F. Donati, G. Beligni, S. Croci, F. Valentino, C. Fallerini, R. Tita, C. Rivera, S. Clark, M. Mencarelli, M. Baldassarri, E. Benetti, S. Furini, E. Frullanti, M. Nabity, A. Auricchio, S. Conticello, A. Renieri, A. Pinto;
Siena, Italy

C17.4 Single-intrathecal delivery of a new AAV9-mediated gene therapy vector provides long-term safe expression of frataxin and prevents neurological and cardiac deficits, neurodegeneration and iron deposition in a Friedreich’s Ataxia mouse model

Eudald Balagué*, D. Cota-González, K. Adrián-Campbell, B. García-Lareu, A. Bosch, J. Coll-Cantí, M. Chillón, I. Sánchez, A. Matilla-Dueñas;
Badalona, Spain

C17.5 HDAC inhibitor CI-994 rescues phenotype in a mouse model of Birk-Barel intellectual disability syndrome

A. Cooper, Tamer Butto, N. Hammer, S. Jagannath, D. Lucia Fend-Guella, J. Akhtar, K. Radyushkin, F. Lesage, J. Winter, S. Strand, J. Roeper, U. Zechner, S. Schweiger;
Mainz, Germany

Chairs:  Conxi Lazaro & Carla Oliveira
Virtual Session Room 2

C18.1 Development of a rapid functional assay on peripheral blood for clinical interpretation of germline TP53 variants and detection of non-coding functional variants

S. Raad, M. Rolain, S. Coutant, C. Derambure, R. Lanos, F. Charbonnier, J. Bou, E. Bouvignies, G. Lienard, S. Vasseur, M. Farrel, O. Ingster, S. Baert-Desurmont, E. Kasper, G. Bougeard, T. Frébourg, Isabelle Tournier;
Rouen, France

C18.2 Are pathogenic germline variants in metastatic melanoma associated with unfavorable survival?

Saskia Biskup, T. Amaral, T. Sinnberg, M. Nieser, P. Martus, C. Garbe, F. Battke, A. Forschner, M. Schulze;
Tuebingen, Germany

C18.3 Germline, somatic and clinical associations with response to Immune Checkpoint Inhibitors and adverse events in a large patient cohort

Stefan Groha*, S. Abou Alaiwi, K. Taraszka, E. Lepisto, M. Manos, O. Rahma, T. Choueiri, M.L. Freedman, D. Schrag, K. Kehl, A. Gusev;
Boston, United States

C18.4 Rare germline variants in the tumor suppressor gene CDH1 are associated with familial glioma

Alisa Förster*, F. Brand, R. Banan, R. Hüneburg, C.A.M. Weber, N. Elyan, C. Previti, J. Kronenberg, U. Beyer, H. Martens, B. Hong, J.K. Krauss, J.H. Bräsen, A. Zimpfer, M. Stangel, A. Samii, S. Wolf, S. Aretz, B. Wiese, C. Hartmann, R.G. Weber;
Hannover, Germany

C18.5 Prostate cancer risk and prognosis for carriers of germline pathogenic variants in disease implicated genes

Niedzica Nadia Camacho Ordonez, L. Dong, A. Matakidou;
Melbourn, Royston, Hertfordshire, United Kingdom

C18.6 Clinical and molecular characterization of 1253 carriers of a deleterious CHEK2 mutation from the German Consortium for Hereditary Breast and Ovarian Cancer (GC-HBOC)

Wisam Habhab, U. Faust, G. Günther, U. Siebers-Renelt, M. Kiechle, C. Ott, N. Dikow, K. Kast, A. Vesper, C. Solbach, N. Harbeck, M. Stiller, A. Gehrig, C. Thomssen, H. Wallaschek, N. Arnold, I. Holzhauser, S. Kaulfuß, A. Volk, W. Janni, C. Engel, R. Schmutzler, O. Rieß, C. Schroeder, K. Bosse;
Tuebingen, Germany

Chairs:   Serena Nik-Zainal & Johannes Zschocke
Virtual Session Room 3

C19.1 One test for all: whole genome sequencing in 62 trios with congenital limb malformation identifies structural variants and new disease genes

J. Elsner, M.A. Mensah, M. Holtgrewe, W. Hülsemann, S. Mundlos, Malte Spielmann;
Berlin, Germany

C19.2 Biallelic mutations inTOGARAM1 cause a novel primary ciliopathy

V. Morbidoni, E. Agolini, K.C. Slept, L. Pannone, D. Zuccarello, E. Grosso, G. Gai, L. Salviati, B. Dallapiccola, A. Novelli, S. Martinelli, Eva Trevisson;
Padova, Italy

C19.3 Biallelic loss-of-function variations in SMO, encoding the key transducer of the Sonic Hedgehog pathway, cause a broad phenotypic spectrum of hedgehogopathies

Thuy L. LE*, Y. Sribudiani, X. Dong, C. Huber, C. Kois, G. Baujat, C.T. Gordon, V. Mayne, L. Galmiche, V. Serre, N. Goudin, M. Zarhrate, C. Bole-Feysot, C. Masson, P. Nitschké, F.W. Verheijen, L. Pais, A. Pelet, S. Sadedin, J.A. Pugh, N. Shur, S.M. White, S.E. Chehadeh, J. Christodoulou, V. Cormier-Daire, R.M.W. Hofstra, S. Lyonnet, T.Y. Tan, T. Attié-Bitach, W.S. Kerstjens-Frederikse, J. Amiel, S. Thomas;
Paris, France

C19.4 Bi-allelic Variants in RALGAPA1 Cause Profound Neurodevelopmental Disability, Muscular Hypotonia, Infantile Spasms, and Feeding Abnormalities

Matias Wagner*, Y. Skorobogatko, B. Pode-Shakked, C.M. Powell, B. Alhaddad, A. Seibt, O. Barel, G. Heimer, C. Hoffmann, L.A. Demmer, Y. Perilla-Young, M. Remke, D. Wieczorek, T. Navaratnarajah, P. Lichtner, D. Klee, H.E. Shamseldin, F.A. Mutairi, E. Mayatepek, T.M. Strom, T. Meitinger, F.S. Alkuraya, Y. Anikster, A.R. Saltiel, F. Distelmaier;
Munich, Germany

C19.5 Functional genomics and extended analyses of unsolved exome-negative cases through the Undiagnosed Diseases Project in Victoria (UDP-Vic)

Tiong Y. Tan, T. Cloney, N.B. Tan, L. Gallacher, J. Elliott, G. Helman, C. Simons, S. Sadedin, L. Pais, A. O’Donnell-Luria, J. Christodoulou, S.M. White;
Parkville, Melbourne, Australia

C19.6 Identification of DNA methylation episignatures for PRC2-related overgrowth syndromes

Michael A. Levy, E. Aref-Eshghi, T.B. Balci, J. Kerkhof, G. Merla, C. Schwartz, B. Sadikovic;
London, Canada

Chairs:  Aurora Pujol & Enza Maria Valente
Virtual Session Room 4

C20.1 An ancestral 10bp repeat expansion in gene encoding component of ECM causes a novel autosomal-recessive peripheral neuropathy

Alistair T. Pagnamenta, Y. Zou, S. Donkervoort, S.B. Neuhaus, R. Maroofian, N. Dominik, H.Y. Yip, A.H. Nemeth, M. O’Driscoll, F. Norwood, J. Rankin, T. Lavin, C. Marini-Bettolo, H. Jungbluth, L. Medne, S.Y. Yum, A.R. Foley, A. Need, Genomics England Research Consortium, J.C. Taylor, C.G. Bönnemann, H. Houlden;
Oxford, United Kingdom

C20.2 Mutations in the Golgi protein GBF1 as a novel cause of distal hereditary motor neuropathy

Natalia Mendoza Ferreira, M. Karakaya, N. Cengiz, D. Beijer, N. Fuhrmann, I. Hölker, B. Schrank, K. Brigatti, C. Gonzaga-Jauregui, E. Puffenberger, G. Wunderlich, P. De Jonghe, T. Deconinck, K. Strauss, J. Baets, B. Wirth;
Cologne, Germany

C20.3 Biallelic JAM2 variants lead to early-onset recessive primary familial brain calcification

Lucia V. Schottlaender*, R. Abeti, Z. Jaunmuktane, C. Macmillan, V. Chelban, B. O’Callaghan, J. McKinley, R. Maroofian, S. Efthymiou, A. Fragkou, R. Forbes, M. Soutar, J. Livingston, B. Kalmar, B. Kalmar, O. Swayne, G. Hotton, A. Pittman, J. Mendes de Oliveira, M. de Grandis, A. Richard-Loendt, F. Launchbury, J. Althonayan, G. McDonnell, A. Carr, S. Khan, C. Beetz, A. Bisgin, S. Tug Bozdogan, A. Begtrup, E. Torti, L. Greensmith, P. Giunti, P. Morrison, S. Brandner, M. Aurrand-Lions, H. Houlden;
Capital federal, Argentina

C20.4 Loss of UGP2 in brain leads to a severe epileptic encephalopathy, emphasizing that bi-allelic isoform specific start-loss mutations of essential genes can cause genetic diseases

Elena Perenthaler*, A. Nikoncuk, S. Yousefi, W.M. Berdowski, M. Alsagob, I. Capo, H.C. van der Linde, P. van den Berg, E.H. Jacobs, D. Putar, M. Ghazvini, E. Aronica, W.F.J. van IJcken, W.G. de Valk, E. Medici–van den Herik, M. van Slegtenhorst, L. Brick, M. Kozenko, J.N. Kohler, J.A. Bernstein, K.G. Monaghan, A. Begtrup, R. Torene, A. Al Futaisi, F. Al Murshedi, F. Al Azri, E. Kamsteeg, M. Mojarrad, A. Eslahi, E. Ghayoor Karimiani, J. Vandrovcova, F. Zafar, N. Rana, K.K. Kandaswamy, J. Hertecant, P. Bauer, D. Colak, S. Efthymiou, H. Houlden, A.M. Bertoli-Avella, R. Maroofian, K. Retterer, A.C. Brooks, N. Kaya, T.J. van Ham, T. Barakat;
Rotterdam, Netherlands

C20.5 Human-lineage-specific genomic elements are enriched within genes implicated in neurodegenerative diseases

Zhongbo Chen*, D. Zhang, R.H. Reynolds, J. Hardy, J. Botía, S.A. Gagliano Taliun, M. Ryten;
London, United Kingdom

C20.6 Full-length RNA sequencing of Alzheimer brain sample using long reads reveals complex alternative splicing patterns

Jenny Ekholm, E. Tseng, T. Hon, J. Underwood;
Menlo Park, United States

Chairs:  Cecilia Lindgren & Matti Pirinen
Virtual Session Room 1

C21.1 A genome-wide association study of sex at birth in 3 million individuals reveals widespread sex-differential participation bias with potential implications for GWAS interpretation

N. Piratsu, M. Cordioli, G. Mignogna, A. Abdellaoui, P. Nandakumar, B. Hollis, M. Kanai, V. Manikandan, P. Della Briotta Parolo, N. Baya, C. Carey, J. Karjalainen, T.D. Als, M.D. Van der Zee, F.R. Day, K.K. Ong, T. Morisaki, E. de Geus, R. Bellocco, Y. Okada, A. Børglum, P. Joshi, A. Auton, D. Hinds, B. Neale, R. Walters, Finngen Study, 23andMe Research Team, iPSYCH Consortium, M.G. Nivard, J.R.B. Perry, Andrea Ganna;
Helsinki, Finland

C21.2 A phenome-wide gene-based collapsing analysis of rare loss-of-function and missense variation in 268,451 UK Biobank exomes

Q. Wang, K. Carss, K. Smith, Slavé Petrovski;
Cambridge, United Kingdom

C21.3 FinnGen – study at its midway: already identifying dozens of novel variants for tens of diseases and traits

Markus Perola;
Helsinki, Finland

C21.4 Discovery, estimation and prediction analysis using a Bayesian survival model for complex traits

Sven E. Ojavee*, D. Trejo-Banos, M. Patxot, K. Fischer, A. Kousathanas, M.R. Robinson;
Lausanne, Switzerland

C21.5 Simultaneous estimation of bi-directional causal effects and heritable confounding from GWAS summary statistics

Liza Darrous*, N. Mounier, Z. Kutalik;
Lausanne, Switzerland

C21.6 Multi-trait genome-wide association analysis of blood pressure identifies 45 additional loci

Claudia P. Cabrera, R. Pazoki, A. Giri, J.N. Hellwege, E. Evangelou, J. Ramírez, L.V. Wain, I. Tzoulaki, T.L. Edwards, P. Elliott, P.B. Munroe, M.R. Barnes, M.J. Caulfield, H.R. Warren, on behalf of the VA Million Veteran Program and the ICBP working group;
London, United Kingdom

Chairs:  Zeynep Tümer & Johannes Zschocke
Virtual Session Room 2

C22.1 Newborn screening for severe combined immunodeficiency (SCID) using combined T cell reception excision circles (TREC)/kappa-deleting element recombination element (KREC) assays and next generation sequencing: diagnostic yield from the new established Swiss programme

Magdeldin Elgizouli, J. Pascal, A. Bahr, S. Prader, D. Drozdof, J. Pachlopnik Schmid, K. Steindl, A. Rauch, J. Reichenbach;
Schlieren, Switzerland

C22.2 Strategies for increasing diagnostic rate in patients with primary immunological disorders within the Genomics England 100,000 Genomes Project

Carme Camps, H. Griffin, K. Engelhardt, Genomics England Research Consortium, S.Y. Patel, S. Hambleton, J.C. Taylor;
Oxford, United Kingdom

C22.3 Dysregulated expression of the long intergenic non-coding RNA (lincRNA), LINC01871, implicated in Sjögren’s Syndrome pathogenesis

M.L. Joachims, B. Khatri, K.L. Tessneer, A.M. Stolarczyk, G.B. Wiley, A. Rasmussen, J.M. Guthridge, J.A. James, R.H. Scofield, K.L. Sivils, I. Adrianto, Christopher J. Lessard;
OKLAHOMA CITY, United States

C22.4 Clonal myelopoiesis in the UK biobank cohort: somatic ASXL1 mutations are strongly associated with smoking history

Ahmed A.Z. Dawoud*, W.J. Tapper, N.C.P. Cross;
Southampton, United Kingdom

C22.5 A genome-wide meta-analysis yields 46 new loci associating with biomarkers of iron homeostasis

Egil Ferkingstad, M.K. Magnusson, S. Bell, A.S. Rigas, E. Allara, G. Bjornsdottir, A. Ramond, E. Sørensen, G.H. Halldorsson, D.S. Paul, K.S. Burgdorf, H.P. Eggertsson, S. Kristmundsdottir, W.J. Astle, C. Erikstrup, J.K. Sigurdsson, D. Vuckovic, V. Tragante, P. Surendran, B. Vidarsson, I. Jonsdottir, T. Hansen, O. Sigurdardottir, H. Stefansson, D. Rye, DBDS Genomic Consortium, J.E. Peters, D. Westergaard, H. Holm, N. Soranzo, K. Banasik, G. Thorleifsson, W.H. Ouwehand, U. Thorsteinsdottir, P. Sulem, A.S. Butterworth, D.F. Gudbjartsson, J. Danesh, S. Brunak, E. Di Angelantonio, H. Ullum, K. Stefansson;
Reykjavik, Iceland

C22.6 Identification of regulators of hematopoietic stem and progenitor cells in vivo in humans using population genetics

Aitzkoa Lopez de Lapuente Portilla, L. Ekhdal, C. Cafaro, Z. Ali, G. Thorleifsson, K. Zemaitis, N. Ugidos Damboriena, E. Johnsson, G. Norddahl, U. Thorsteinsdottir, J. Larsson, K. Stefansson, B. Nilsson;
Lund, Sweden

Chairs:  Francesca Forzano & Ramona Moldovan
Virtual Session Room 3

C23.1 Helping very young children understand inherited cancer predisposition syndromes using bibliotherapy

G. Schlub, A. Crook, J. Fleming, Kristine Barlow-Stewart, J. Kirk, K. Tucker, S. Greening;
Sydney, Australia

C23.2 Towards personalized genetic counselling: exploring subgroups among counselees based on different facets of empowerment before the first visit

Jan Voorwinden*, E. Birnie, M. Plantinga, M. Ausems, N. Knoers, M. Velthuizen, A. Lucassen, I. van Langen, A. Ranchor;
Groningen, Netherlands

C23.3 Exploring patient deliberation prior to predictive genetic testing in the absence of immediate clinical utility

Lisa M. Ballard, S. Doheny, A.M. Lucassen, A.J. Clarke;
Southampton, United Kingdom

C23.4 Negotiating autonomy and interdependence with family: how young people and health professionals navigate genetic testing for Li-Fraumeni syndrome

Rowan Forbes Shepherd*, L.A. Keogh, A.V. Werner-Lin, M.B. Delatycki, L.E. Forrest;
Melbourne, Australia

C23.5 Exploring outcomes from the Deciphering Developmental Disorders study

H. Copeland, E. Kivuva, G. Hall, T. DDD Study, C. Wright;
Exeter, United Kingdom

C23.6 Improving the communication of genomics results to patients and families with rare diseases using Experience-Based Co-Design (EBCD)

A. Costa, Vera Frankova, E. Alexander, A. Arellanesová, V. Bros-Facer, J. Clayton-Smith, G. Gumus, M. Havlovicova, A. Hunter, M. Macek, A. Metcalfe, C. Patch, R. Pourová-Kremlíková, M. Pritchard, G. Robert, L. Roberts;
Prague, Czech Republic

Chairs:  Joris Veltman & Alexandre Reymond
Virtual Session Room 4


A novel disorder involving dyshematopoiesis, inflammation and HLH due to aberrant CDC42 function

Simona Coppola, M.T. Lam, O.H. Krumbach, G. Prencipe, I. Insalaco, C. Cifaldi, I. Brigida, E. Zara, S. Scala, S. Martinelli, S. Martinelli, M. Di Rocco, A. Pascarella, M. Niceta, F. Pantaleoni, A. Ciolfi, F. Carisey, M. Akbarzadeh, L. Farina, L. Pannone, H.C. Erichsen, A.C. Horne, Y. Bryceson, L. Torralba-Raga, K. Ramme, A. Finocchi, F. Locatelli, C. Cancrini, A. Aiuti, M.R. Ahmadian, J.S. Orange, F. De Benedetti, M. Tartaglia;
Rome, Italy


Unraveling the genetic architecture of autosomal recessive Charcot-Marie-Tooth neuropathies

Camila Armirola, K. Peters, E. de Vriendt, S. Amor-Barris, A. Jordanova;
Antwerp, Belgium


Loss of costameric supervillin causes myopathy with myofibrillar disorganization and autophagic vacuoles

C. Hedberg-Oldfors, R. Meyer, K. Nolte, Y.A. Rahim, C. Lindberg, K. Karason, I.J. Thuestad, K. Visuttijai, M. Geijer, M. Begemann, F. Kraft, E. Lausberg, L. Hitpaß, R. Götzl, E.J. Luna, H. Lochmüller, S. Koschmieder, M. Gramlich, B. Gess, M. Elbracht, J. Weis, I. Kurth, A. Oldfors, Cordula Knopp;
Aachen, Germany


Genome wide methylation profiling, EpiSign, as a diagnostic test

Marielle Alders, P. Henneman, E. Aref-Eshghi, A. Venema, J. Kerkhof, B. Sadikovic, M. Mannens;
Amsterdam, Netherlands


The landscape of BRCA1 and BRCA2 variants from 300,000 individuals in the UK Biobank population sampling

Zara Ghazoui;
Cambridge, United Kingdom


Nanopore-sequencing-based high-resolution karyotyping of AML patients

Florian Kraft, P. Krüger, S. Koschmieder, E. Jost, M. Crysandt, I. Kurth;
Aachen, Germany


Classification of ATM variants identified in Spanish patients with suspicion of hereditary cancer

L. Feliubadaló, M. Santamariña Peña, L.M. Porras, A. Moles-Fernández, A.T. Sánchez, A. Blanco, O. Diez, S. Gutiérrez-Enríquez, M. de la Hoya, A. Lopez-Novo, A. Osorio, M. Pineda, D. Rueda, C. Ruiz-Ponte, A. Vega, I.J. Molina, X. de la Cruz,
Conxi Lázaro;
Hospitalet de Llobregat, Spain


Reduced male reproductive success drives selective constraint on human genes

Eugene J. Gardner, M.D.C. Neville, K.E. Samocha, M.E.K. Niemi, K.J. Barclay, M. Kolk, G. Kirov, H.C. Martin, M.E. Hurles;
Hinxton, United Kingdom


Widespread sexual differences in genetic architecture in UK Biobank

Elena Bernabeu, O. Canela-Xandri, K. Rawlik, A. Talenti, J. Prendergast, A. Tenesa;
Edinburgh, United Kingdom


Profiling the chromatin landscape of early neurodevelopment using scATAC-seq

Camiel C. Mannens, L. Hu, E.P. Braun, P. Lönnerberg, S. Linnarsson;
Solna, Sweden

Chairs: Thierry Voet & Malte Spielman
Virtual Session Room 5


Deciphering genomic inversions

C. M. Grochowski1, M. Pettersson2, J. Eisfeldt2, M. Gandhi1,3, D. Pehlivan1, C. Gonzaga-Jauregui4, M. Withers1, P. Stankiewicz1,5, A. C. V. Krepischi6, J. R. Lupski1, A. Lindstrand2, C. M. B. Carvalho1;
1Baylor College of Medicine, Houston, TX, United States, 2Karolinska Institutet, Stockholm, Sweden, 3University of Texas MD Anderson Cancer Center, Houston, TX, United States, 4Regeneron, Tarrytown, NY, United States, 5Baylor Genetics, Houston, TX, United States, 6University of São Paulo, SP, Brazil.


Polymorphic inversions underlie the shared genetic susceptibility of obesity-related diseases

J. R. Gonzalez1, C. Ruiz1, A. Caceres1, I. Moran2, M. Lopez1, L. Alonso2, I. Tolosana1, M. Guindo-Martinez3, J. M. Mercader3, T. Esko4, D. Torrents2, J. Gonzalez5, L. A. Perez-Jurado5;
1Barcelona Institute for Global Health, BARCELONA, Spain, 2Barcelona Supercomputing Center, BARCELONA, Spain, 3Broad Institute, BOSTON, MA, United States, 4University of Tartu, BARCELONA, Estonia, 5Universitat Pompeu Fabra, BARCELONA, Spain.


Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals

E. V. Feofanova, the Blood Pressure‐International Consortiumof Exome chip Studies (BP‐ICE), CHARGE consortium, CHD Exome+, Exome BP, GoT2D:T2Dgenes, deCODE, the Million Veteran Program (MVP);
Human Genetics Center, The University of Texas Health Science Center at Houston, Houston, TX, United States.


Multi-Omics integration for molecular diagnostics of mendelian disorders

R. Kopajtich1,2, D. Smirnov1,2, S. Loipfinger3, C. Meng4, D. Ghezzi5, K. Murayama6, J. A. Mayr7, P. Freisinger8, M. D. Metodiev9, A. Rötig9, T. Klopstock10, G. F. Hoffmann11, R. Santer12, F. Distelmaier13, R. Olsen14, D. Piekutowska-Abramczuk15, P. Verloo16, C. Lamperti5, J. Gagneur3, C. Ludwig4, H. Prokisch1,2;
1Institute of Human Genetics, Technical University Munich, München, Germany, 2Institute of Neurogenomics, Helmholtz Center Munich, Munich, Germany, 3Department of Informatics, Technical University Munich, Garching, Germany, 4Bavarian Center for Biomolecular Mass Spectrometry, BayBioMS, Technical University Munich, Freising, Germany, 5Unit of Molecular Neurogenetics, Istituto Neurologico ‘‘Carlo Besta, Milan, Italy, 6Department of Metabolism, Chiba Children’s Hospital, Chiba, Japan, 7Department of Paediatrics, Paracelsus Medical University, Salzburg, Austria, 8Department of Pediatrics, Klinikum Reutlingen, Reutlingen, Germany, 9INSERM U1163, Université Paris, Institut Imagine, Paris, France, 10Department of Neurology, Friedrich-Baur-Institute, Ludwig-Maximilians-University, Munich, Germany, 11Department of General Pediatrics, University Hospital Heidelberg, Heidelberg, Germany, 12University Medical Center Eppendorf, Hamburg, Germany, 1313Department of General Pediatrics, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany, 1414Research Unit for Molecular Medicine, Aarhus University and University Hospital, Aarhus N, Denmark, 15Department of Medical Genetics, The Children’s Memorial Health Institute, Warsaw, Poland, 16Department of Internal Medicine and Paediatrics, Ghent University Hospital, Ghent, Belgium.


Impaired complex I repair causes recessive Leber’s hereditary optic neuropathy

S. L. Stenton1,2, N. Sheremet3, C. Catarino4, N. Andreeva3, Z. Assouline5, P. Barboni6, O. Barel7, I. Bychkov8, L. Caporali9, P. Charbel Issa10, P. Freisinger11, S. Gerber12, D. Ghezzi13, J. Heidler14, M. Hempel15, E. Heon16, Y. Itkis17, E. Javasky7, J. Kaplan12, R. Kopajtich1,2, C. Kornblum18, R. Kovacs-Nagy19,1, T. Krylova8, W. Kunz20, C. La Morgia9, C. Lamperti13, C. Ludwig21, P. Malacarne22, J. Mayr23, J. Meisterknecht14, T. Nevinitsyna3, F. Palombo9, B. Pode-Shakked24, M. Shmelkova3, M. Tzadok24, A. van der Ven15, C. Vignal-Clermont25, M. Wagner1, E. Zakharova8, N. Zhorzholadze3, J. Rozet12, V. Carelli9, P. Tsygankova8, T. Klopstock4, I. Wittig14, H. Prokisch1,2;
1Institute of Human Genetics, Technische Universität München, München, Germany, 2Institute of Neurogenomics, Helmholtz Zentrum München, München, Germany, 3Federal State Budgetary Institution of Science “Research Institute of Eye Diseases”, Moscow, Russian Federation, 4Department of Neurology, Friedrich-Baur-Institute, University Hospital of the Ludwig-Maximilians-Universität München, München, Germany, 5Fédération de Génétique et Institut Imagine, Université Paris Descartes, Hôpital Necker Enfants Malades, Paris, France, 6Scientific Institute San Raffaele, Milan, Italy, 7Genomics Unit, Sheba Cancer Research Center, Sheba Medical Center, Tel-Hashomer, Israel, 8Research Centre for Medical Genetics, Moscow, Russian Federation, 9IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy, 10Oxford Eye Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom, 11Department of Pediatrics, Klinikum am Steinenberg, Reutlingen, Germany, 12Laboratory genetics in ophthalmology (LGO), INSERM UMR1163 – Institute of genetic diseases, Imagine, Paris, France, 13Unit of Medical Genetics and Neurogenetics, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy, 14Functional Proteomics, SFB815 Core Unit, Medical School, Goethe University, Frankfurt am Main, Germany, 15Institute of Human Genetics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany, 16The Hospital for Sick Children, Department of Ophthalmology and Vision Sciences, The University of Toronto, Toronto, ON, Canada, 17Research Centre for Medical Genetics, Moscow, Moscow, Russian Federation, 18Department of Neurology, University Hospital Bonn, Bonn, Germany, 19Department of Medical Chemistry, Molecular Biology and Pathobiochemistry, Semmelweis University, Budapest, Hungary, 20Department of Experimental Epileptology and Cognition Research, University of Bonn, Bonn, Germany, 21Bavarian Center for Biomolecular Mass Spectrometry (BayBioMS), Technische Universität München, München, Germany, 22Institute for Cardiovascular Physiology, Goethe-University, Frankfurt am Main, Germany, 23Department of Pediatrics, Salzburger Landeskliniken and Paracelsus Medical University Salzburg, Salzburg, Austria, 24Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel, 25Ophthalmology Department, Centre National d’Ophtalmologie des Qinze-Vingts, Paris, France.


WES profiling of COVID-19

A. Renieri1,2, E. Benetti3, F. Montagnani3,4, R. Tita2, C. Fallerini1, S. Amitrano2, M. Bruttini2, G. Doddato1, A. Giliberti1, F. Valentino1, S. Croci1, L. Di Sarno1, F. Fava1,2, M. Baldassarri1, A. Tommasi1,2, M. Palmieri1, A. Emiliozzi3,4, M. Fabbiani4, B. Rossetti4, G. Zanelli3,4, L. Bergantini5, M. D’Alessandro5, P. Cameli5, D. Bennet5, F. Anedda6, S. Marcantonio6, S. Scolletta6, F. Franchi6, M. Mazzei7, E. Conticini8, L. Cantarini9, B. Frediani10, D. Tacconi11, M. Feri12, R. Scala13, A. Ognibene14, G. Spargi15, C. Nencioni16, G. Caldarelli17, M. Spagnesi18, A. Canaccini19, E. Frullanti1, I. Meloni1, M. Mencarelli2, C. Lo Rizzo2, A. Pinto2, E. Bargagli5, M. Mandalà20, S. Furini3, F. Mari1,2;
1Medical Genetics, University of Siena, Siena, Italy, 2Genetica Medica, Azienda Ospedaliera Universitaria Senese, Siena, Italy, 3Dept of Medical Biotechnologies, University of Siena, Siena, Italy, 4Dept of Specialized and Internal Medicine, Tropical and Infectious Diseases Unit, Siena, Italy, 5Unit of Respiratory Diseases and Lung Transplantation, Department of Internal and Specialist Medicine, University of Siena, Siena, Italy, 6Dept of Emergency and Urgency, Medicine, Surgery and Neurosciences, Unit of Intensive Care Medicine, Siena University Hospital, Siena, Italy, 7Dept of Medical, Surgical and Neuro Sciences, Diagnostic Imaging, University of Siena, Azienda Ospedaliera Universitaria Senese, Siena, Italy, 8Rheumatology Unit, Department of Medicine, Surgery and Neurosciences, University of Siena, Policlinico Le Scotte, Siena, Italy, 9Dept of Medical Sciences, University of Siena, Siena, Italy, 10Research Center of Systemic Autoinflammatory Diseases and Behçet’s Disease and Rheumatology-Ophthalmology Collaborative Uveitis Center, Department of Medical Sciences, Surgery and Neurosciences, University of Siena, Siena, Italy, 11Dept of Specialized and Internal Medicine, Infectious Diseases Unit, San Donato Hospital Arezzo, Arezzo, Italy, 12Dept of Emergency, Anesthesia Unit, San Donato Hospital, Arezzo, Italy, 13Dept of Specialized and Internal Medicine, Pneumology Unit and UTIP, San Donato Hospital, Arezzo, Italy, 14Clinical Chemical Analysis Laboratory, San Donato Hospital, Arezzo, Italy, 15Dept of Emergency, Anesthesia Unit, Misericordia Hospital, Grosseto, Italy, 16Dept of Specialized and Internal Medicine, Infectious Diseases Unit, Misericordia Hospital, Grosseto, Italy, 17Clinical Chemical Analysis Laboratory, Misericordia Hospital, Grosseto, Italy, 18Dept of Prevention, ASL South-East Tuscany, ASL South-East Tuscany, Italy, 19Territorial Scientific Technician Department, ASL South-East Tuscany, ASL South-East Tuscany, Italy, 20Otolaryngology Unit, University of Siena, Siena, Italy.

Chairs:   Martin Kircher & Nicola Brunetti-Pierri
Virtual Session Room 1

C26.1 Electrical impedance detection based GenapSys sequencer enables diverse genomic applications

Saurabh Paliwal, A. Nabi, M. Fallahi, M.R. Barmi, M. Jouzi, S. Stern, X. Gomes, H. Nezamfar, E. LoPrete, B. Dong, P. Kenney, K.B. Parizi, H. Rategh, S. Sankar, H. Esfandyarpour;
Redwood City, United States

C26.2 A bespoke gene-to-patient approach uplifts novel gene discovery for rare disease diagnostics

E. G. Seaby*, D. Smedley, R. Scott, M. Caulfield, D. Baralle, H. L. Rehm, A. O’Donnell-Luria, S. Ennis;
Southampton, United Kingdom

C26.3 Analysis of Mendelian phenotypes through mouse embryo viability screening

Pilar Cacheiro, S.A. Murray, V. Muñoz-Fuentes, H. Westerberg, M.E. Dickinson, A. Mallon, T.F. Meehan, D. Smedley, the International Mouse Phenotyping Consortium;
London, United Kingdom

C26.4 Patient-derived retinal organoids to model retinitis pigmentosa 1 (RP1)

Patricia Berber*, A. Milenkovic, C. Brandl, B.H.F. Weber;
Regensburg, Germany

C26.6 Next generation cytogenetics: genome-imaging improves structural variant detection for constitutional chromosomal aberrations

Kornelia Neveling, T. Mantere, E. Kater-Baats, R. van Beek, M. Oorsprong, S. Vermeulen, M. Pauper, D. Olde Weghuis, M. Stevens-Kroef, G. van der Zande, D. Smeets, A. Hoischen;
Nijmegen, Netherlands

Chairs:  Michael Speicher & Elfride de Baere
Virtual Session Room 2

C27.1 NCBI ALFA: Providing Sequence Variation Resource from 1 Million dbGaP Subjects

Lon Phan, NCBI dbSNP, NCBI dbGaP;
Bethesda, United States

C27.2 Predicting the effects of structural variants in the human genome

Philip Kleinert*, M. Kircher;
Berlin, Germany

C27.3 RNA secondary structure mediated by Alu insertion as a novel disease-causing mechanism

Emmanuelle Masson, S. Maestri, D.N. Cooper, C. Férec, J.M. Chen;
Brest, France

C27.4 Increased mutation rates and genome variation at active spermatogonial regulatory sites

Vera B. Kaiser, L. Talmane, Y. Kumar, F. Semple, M. MacLennan, Deciphering Developmental Disorders Study, D.R. FitzPatrick, M.S. Taylor, C.A. Semple;
Edinburgh, United Kingdom

C27.5 Resolving complex structural variants in recurrent brain tumors

K. Okonechnikov, J. Hübner, O. Chapman, A. Chakraborty, M. Pagadal, R. Bumb, S. Chandran, K. Kraft, R. Hidalgo, S. Mundlos, R. Wechsler-Reya, N. Coufal, M. Levy, J. Crawford, K. Pajtler, D. Reid, A. Schmitt, H. Carter, F. Ay, J. Dixon, J. Mesirov, S.M. Pfister, M. Kool, Lukas Chavez;
San Diego, United States

Chairs:  Zeynep Tümer & Aurora Pujol
Virtual Session Room 3

C28.1 Pathogenic variants in RLIM/RNF12 lead to syndromic X-linked intellectual disability and congenital, neurologic and behavior disorders

Suzanna G.M. Frints, A. Ozanturk, G. Rodriguez Criado, U. Grasshoff, M. Field, S. Manouvrier-Hanu, S. Hickey, K. Gripp, C. Bauer, C. Schroeder, A. Toutain, T. Mihalic Mosher, B.J. Kelly, P. White, A. Dufke, S. Moon, D.C. Koboldt, E. Gerkes, A. van Haeringen, C. Ruivenkamp, C. Mignot, B. Keren, A. Müller, S. Waldmüller, M. Blandfort, U. Kordaß, K. Gardner, A. Trimouille, K.E.P. van Roozendaal, S.A. Haas, L. Murray, E. Haan, R. Carroll, J. Liebelt, L. Hobson, M. De Rademaeker, H. Brunner, J. Glatz, K. Devriendt, J. Vermeesch, M. Raynaud, O. Riess, J. Gribnau, N. Katsanis, P. Bauer, J. Gecz, C. Golzio, C. Gontan, V. Kalscheuer;
Maastricht, Netherlands

C28.2 De-novo and Biallelic pathogenic variants in NARS1 cause neurodevelopmental delay due to dominant negative and partial loss of function effect

Emer O’Connor, A. Manole, S. Efthymiou*, M. Mendes, M. Jennings, D. Jenkins, M. Lopez, R. Maroofian, V. Salpietro, S. Antonarakis, J. Vincent, T. B. Haack, F. Distelmaier, R. Horvath, J. Gleeson, H. Becker, J. Mandel, D. Koolen, H. Houlden;
London, United Kingdom

C28.3 Biallelic loss-of-function variants in TBC1D2B cause a neurodevelopmental disorder with seizures and gingival overgrowth

Frederike L. Harms*, P. Parthasarathy, D. Zorndt, M. Alawi, S. Fuchs, B.J. Halliday, C. McKeown, H. Sampaio, N. Radhakrishnan, S.K. Radhakrishnan, R. Sachdev, S.P. Robertson, S. Nampoothiri, K. Kutsche;
Hamburg, Germany

C28.4 De novo pathogenic variants in CSNK2B cause a new intellectual disability-craniodigital syndrome distinguished from Poirier-Bienvenu neurodevelopmental syndrome

Maria Asif*, E. Kaygusuz, M. Shinawi, A. Nickelsen, J. Hochscherf, D. Lindenblatt, A.A. Noegel, S. Tinschert, K. Niefind, P. Fortugno, J. Jose, F. Brancati, P. Nürnberg, M.S. Hussain;
Cologne, Germany

C28.5 Biallelic and monoallelic variants in PLXNA1 cause a syndromic disorder with neurodevelopmental and oculo-cerebral anomalies

Gabriel C. Dworschak*, J. Punetha, J.C. Kalanithy, E. Mingardo, H.B. Erdem, Z.C. Akdemir, E. Karaca, T. Mitani, D. Marafi, J.M. Fatih, S.N. Jhangiani, J.V. Hunter, T. Dakal, B. Dhabhai, O. Dabbagh, H.S. Alsaif, F.S. Alkuraya, R. Maroofian, H. Houlden, S. Efthymiou, N. Dominik, V. Salpietro, T. Sultan, S. Haider, F. Bibi, H. Thiele, J. Hoefele, K.M. Riedhammer, M. Wagner, I. Guella, M. Demos, B. Keren, J. Buratti, P. Charles, C. Nava, E. Valkanas, L.B. Waddell, K.J. Jones, E.C. Oates, S.T. Cooper, D. MacArthur, R.E. Schnur, G.E. Hoganson, J.E. Burton, M. McEntagart, D. Pehlivan, J.E. Posey, J.R. Lupski, H. Reutter;
Bonn, Germany

C28.6 Mutations in Gemin5 cause developmental delay, motor dysfunction and cerebellar atrophy

Udai Pandey;
Pittsburgh, United States

Chairs:  Doris Steinemann & Johannes Zschocke
Virtual Session Room 1

C29.1 Homozygous loss-of-function mutations in CCDC134 are responsible for a severe form of osteogenesis imperfecta

Johanne Dubail, P. Brunelle, G. Baujat, C. Huber, M. Doyard, C. Michot, P. Chavassieux, A. Khairouni, V. Topouchian, S. Monnot, E. Koumakis, V. Cormier-Daire;
Paris, France

C29.2 Hypomorphic variants in the replication complex member GINS3 result in a Meier Gorlin phenotype

Peter Kannu, E. Campos, H. Wurtele, K. Ahmed, R. Shaheen, M. McQuaid, K. Kernohan, K. Boycott, Z. Alhassnan, F. Alkuraya;
Toronto, Canada

C29.3 Homozygous EMILIN1 loss-of-function variants impair both elastin and collagen fiber formation and cause a novel entity with arterial tortuosity and osteopenia

Aude Beyens*, C. Adamo, E. Yilmaz Gulec, A. Gezdirici, P. Bonaldo, H. Bornaun, E. Brauchle, J. Brinckmann, W.P. Devine, B. Gangaram, T. Sasaki, K. Schenke-Layland, S. Symoens, A. Tam, G. Sengle, B. Callewaert;
Ghent, Belgium

C29.4 Transcriptional single-cell atlas of human limb malformation candidate genes

Cesar A. Prada-Medina*, G. Cova, J. Glaser, C. Dietrich, J. Henck, S. Mundlos, M.A. Mensah, M. Spielmann;
Berlin, Germany

C29.5 Tendon-to-bone attachment cells are bi-fated are regulated by shared enhancers KLF transcription factors

S. Kult, Tsviya Olender, M. Osterwalder, S. Krief, R. Blecher-Gonen, S. Ben-Moshe, L. Farack, H. Keren-Shaul, D. Leshkowitz, T.M. Salame, T.D. Capellini, S. Itzkovitz, I. Amit, A. Visel, E. Zelzer;
Rehovot, Israel

C29.6 Identifying targets for osteoporosis via whole exome sequencing and CRISPR-Cas9

S. Zhou, L. Laurent, J. P. Kemp, V. Forgetta, J. Morris, A. Pramatarova, P. I. Croucher, J. Bassett, D. Goltzman, D. M. Evans, J. Richards;
Montreal, Canada

Chairs:  Vita Dolzan & Matti Pirinen
Virtual Session Room 2

C30.1 Using reference-fixed principal components to improve polygenic risk score prediction

Olivier Naret*, J. Fellay;
Lausanne, Switzerland

C30.2 The Polygenic Score (PGS) Catalog: an open database to enable reproducibility and systematic evaluation

Samuel A. Lambert*, L. GIl, S. Jupp, M. Chapman, H. Parkinson, J. Danesh, J.A.L. MacArthur, M. Inouye;
Cambridge, United Kingdom

C30.3 Polygenic risk, breast cancer susceptibility genes, and breast cancer over the life course

Nina Mars*, E. Widén, T. Meretoja, S. Kerminen, M. Pirinen, P. Palta, A. Palotie, J. Kaprio, H. Joensuu, M. Daly, S. Ripatti;
Helsinki, Finland

C30.4 Genetic assessment of age-associated fracture risk

Carolina Medina-Gomez*, K. Trajanoska, C. Fan, O.A. Andreassen, M. Zillikens, A.M. Dale, A.G. Uitterlinden, T.M. Seibert, F. Rivadeneira;
Rotterdam, Netherlands

C30.5 Integrative analysis of the plasma proteome and polygenic risk of cardiometabolic disease

Scott C. Ritchie*, Y. Liu, S.A. Lambert, B.G. Drew, A.C. Calkin, A.S. Butterworth, J. Danesh, M. Inouye;
Cambridge, United Kingdom

C30.6 Genotyping On ALL patients (GOALL); clinical implementation of high-throughput genotyping arrays

J. van Rooij, A. Verkerk, B. Sedaghati-khayat, L. Broer, J. de Vries, G. van Dijk, J. van Meurs, A. Uitterlinden;
Rotterdam, Netherlands

Chairs:  Sam Riedijk & Enza Maria Valente
Virtual Session Room 3

C31.1 “It’s probably nothing, but⋯” Couples’ experiences of pregnancy following a uncertain prenatal genetic result

Stina Lou, K. Lomborg, C. Lewis, S. Riedijk, O. Petersen, I. Vogel;
Aarhus, Denmark

C31.2 Additional Genomic Findings: towards a feasible, effective model of care

E. Lynch, M. Martyn, L. Lee, A. Kanga-Parabia, R. Weerasuriya, R. Tytherleigh, Clara L. Gaff;
Parkville, Australia

C31.3 Analysis of laboratory exome sequencing reporting practices using a ‘virtual patient’

Danya F. Vears, M.G. Elferink, M. Kriek, P. Borry, K.L. van Gassen;
Leuven, Belgium

C31.4 Knowledge, attitudes and preparedness for polygenic risk testing in clinical practice: a cross-sectional survey of health professionals

Amelia K. Smit*, A.E. Cust, K. Dunlop, M. Young, B. Meiser, J. Tiller, T. Yanes;
Sydney, Australia

C31.5 Impact of the discussion of uncertainty on former counselees’ outcomes. An experimental vignettes study

Niki Medendorp, M. Hillen, C. Aalfs, A. Stiggelbout, E. Smets;
Amsterdam, Netherlands

C31.6 Primary Care Genomics: A roadmap for curriculum change and educational resource development

J. Hayward, I. Rafi, S. Simpson, E. Miller, A. Seller, Michelle Bishop;
Birmingham, United Kingdom

Concurrent Symposia

Chairs:   Yasemin Alanay & Maris Laan
Virtual Session Room 1

S01.1 Prenatal Genomic Approach to Genetic Diseases of Bone

Deborah Krakow;
United States

S01.2 Pandora’s Pregnancy – A new Era for Prenatal Genetic Testing

Yeal Hashiloni‐Dolev;

S01.3 Prenatal Exome and Genome Sequencing: The PAGE Study and Future Perspectives

Mark Kilby;
United Kingdom

Chairs:   Michael Speicher & Serena Nik-Zainal
Virtual Session Room 2

S02.1 Methylation Patterns of Plasma DNA in Health and Disease

Yuval Dor;

S02.2 Fragmentation of Plasma Cell-Free DNA for Early Detection of Cancer

Victor E. Velculescu;
United States

S02.3 Circulating Tumor Cells and Minimal Residual Disease, Latest Advances

Catherine Alix-Panabières;

Chairs:   Matti Pirinen & Zoltan Kutalik
Virtual Session Room 3

S03.1 Why We Should Study African Genomic Variation

Ambroise Wonkam;
South Africa

S03.2 Genomes of Archaic Humans and their Contribution to Modern Humans

Janet Kelso;

S03.3 Inferring Ancestry of Everyone

Jerome Kelleher
United Kingdom

Chairs: Celine Lewis & Sam Riedijk
Virtual Session Room 4

S04.1 The Patient’s Role in New Disease Gene Discovery

Christian Schaaf;

S04.2 Experiences with public engagement: Estonian Biobank’s example

Annely Allik;

S04.3 My DNA, whose business is it anyway? A Citizen Forum on the Societal Impact of Genomics

Wannes Van Hoof;

Chairs:  Malte Spielmann & Thierry Voet
Virtual Session Room 1

S05.1 Embryo-scale, single-cell spatial transcriptomics

Cole Trapnell;
United States

S05.2 Cellular drivers of injury response and regeneration in the zebrafish heart

Jan Philipp Junker;

S05.3 Transcriptome-Scale Super-Resolved Imaging in Tissues by RNA SeqFISH

Long Cai;
United States

Chairs:  Zeynep Tümer & Nicola Brunetti-Pierri
Virtual Session Room 2

S06.1 Nonsense Mediated Decay in Neuronal Development and Disease

Miles Wilkinson
United States

S06.2 Genetic Compensation

Didier Stainier

S06.3 Alternativa Splicing and Nonsense-Mediated Decay

Liana Lareau
United States

Chairs:   Cecilia Lindgren & Zoltan Kutalik
Virtual Session Room 3

S07.1 Large Scale Dissection of the Genetic Architecture of Molecular and Cellular Traits in Adipocytes

Melina Claussnitzer;

S07.2 Functional Approaches to Gain Insights Into Type 2 Diabetes Loci

Anna Gloyn;
United Kingdom

S07.3 Understanding Blood Cell Production in Health and Disease – From Disease Gene to Mechanism

Vijay Sankaran;
United States

Chairs:   Karin Writzl & Vita Dolzan
Virtual Session Room 4

S08.1 Challenges in Diagnostic Sequencing for Inherited Cardiac Conditions

Roddy Walsh;
United Kingdom

S08.2 RNAs in cardiovascular system – the potential use as biomarkers and as therapeutic carriers

Thomas Thum;

S08.3 Identification and Characterization of Novel Microproteins in the Human Heart

Sebastiaan van Heesch;

Chairs:  Elfride de Baere & Cecilia Lindgren
Virtual Session Room 1

S09.1 From digenic predictions to oligogenic networks via a new predictive approach

Tom Lenaerts;

S09.2 Common Variants Determine Quasi-Mendelian Inheritance of Rare Diseases

Carlo Rivolta;

S09.3 Resolution of Disease Phenotypes Resulting from Multilocus Genomic Variation

Jennifer Posey;
United States

Chairs:   Jose Luis Costa & Thierry Voet
Virtual Session Room 2

S10.1 Single-Cell RNA-Seq on Tumor Microenvironment in Lung Cancer

Bernard Thienpont;

S10.2 Single-Cell Analysis in Tumour Progression

Alex Swarbrick;

S10.3 Single cell to understand AML progression

Alexander Perl;
United States

Chairs:  Maris Laan & Malte Spielmann
Virtual Session Room 3

S11.1 The unsung hero: The essential role of the placenta for development and lifelong health

Myriam Hemberger;

S11.2 Genetics of Recurrent Hydatidiform Moles: Novel Findings and Patient Counselling

Rima Slim;

S11.3 Organoids to understand pregnancy disorders

Graham J. Burton;
United Kingdom

Chairs:   Francesca Forzano & Ramona Moldovan
Virtual Session Room 4

S12.1 The state of the science of heritable human genome editing and ethical concerns

Michele Ramsay;
South Africa

S12.2 Addressing Misuse of Science in Surveillance

Yves Moreau;

S12.3 Whole genome sequencing in Health Care 2.0: Testing, Tailoring, Targeting

Martina Cornel;
The Netherlands

Chairs:   Nicola Brunetti-Pierri & Yasemin Alanay
Virtual Session Room 5

S13.1 The Lysosome in the Control of Cell Metabolism

Andrea Ballabio;

S13.2 Complex cellular pathology in lysosomal disorders: insights from Niemann-Pick disease type C

Frances Platt;
United Kingdom

S13.3 Therapy of Lysosomal Storage Disorders – Lessons from Fabry Disease

Raphael Schiffmann;
United States

Chairs:  Joris Veltman & Teri Manolio
Virtual Session Room 1

S14.1 Polygenic risk scores in the clinic: Challenges and opportunities

Michael Inouye;
United Kingdom

S14.2 Polygenic Risk Scores, How to Use?

Mark Daly;

S14.3 Polygenic risk scores and their use in the clinic

Amit Khera;
United States

S14.4 Improving Polygenic Risk Scores for Clinical Applications

Krista Fischer;

Chairs:  Martin Kircher & Michael Speicher
Virtual Session Room 2

S15.1 Detection of Structural Variation and Haplotype-Aware Genome Assembly

Tobias Marschall;

S15.2 Improving the Detection and Genotyping of Structural Variation

Birte Kehr;

S15.3 Annotation and Curation of High-Confidence Structural Variants

Aaron Quinlan;
United States

Chairs:  Doris Steinemann & Jose Luis Costa
Virtual Session Room 3

S16.1 Inherited Myeloid Malignancies

Jude Fitzgibbon;
United Kingdom

S16.2 Genetics and Mechanisms of Acute Lymphoblastic Leukemia

Adolfo Ferrando;
United States

S16.3 Somatic versus Germline Alterations in Leukemia

Cristina Mecucci;

Chairs: Valerie Cormier-Daire & Yasemin Alanay
Virtual Session Room 4

S17.1 Cornelia de Lange Spectrum: does deep phenotyping help?

Feliciano Ramos;

S17.2 Genetic causes and overlapping mechanisms in the spectrum of Cornelia de Lange syndrome

Frank Kaiser;

S17.3 Post-Zygotic Mutation as a Cause of Typical Cornelia De Lange Syndrome

David FitzPatrick;
United Kingdom

Chairs:  Serena Nik-Zainal & Christian Gilissen
Virtual Session Room 1

S18.1 Somatic Mutation and Clonal Expansions in Human Tissues

Inigo Martincorena;
United Kingdom

S18.2 Somatic Genetic Rescue in Mendelian Haematopoietic Diseases

Patrick Revy

S18.3 Somatic Mutations and Regeneration in Chronic Liver Disease

Hao Zhu;
United States

Chairs:  Sam Riedijk & Yasemin Alanay
Virtual Session Room 2

S19.1 Array-based mutation testing, PRS, PGx, and return of results in a hospital setting: the GOALL project

Andre Uitterlinden;
The Netherlands

S19.2 Empirical Evidence in Preventive Genomics: MedSeq, BabySeq and Beyond

Carrie Blout;
United States

S19.3 The challenges facing clinical-research hybrid practices

Anneke Lucassen;
United Kingdom

Chairs:  Matti Pirinen & Cecilia Lindgren
Virtual Session Room 3

S20.1 Combining omics data with GWAS results

Alexander Gusev;
United States

S20.2 A Bayesian Framework for Joint Fine-Mapping with Applications to Immune-Mediated Diseases

Jennifer Asimit;
United Kingdom

S20.3 Integrative Transcriptomic Analysis in Neurodegenerative Diseases

Towfique Raj;
United States