Workshop: An overview of public resources for gene-disease association and sequence and copy number variant interpretation

In this workshop, participants will learn about (and have hands-on experience with) new or newly updated resources that can aid in the interpretation of genomic data, including:

1. the Gene Curation Coalition (GenCC) Database;
2. gnomAD: The Genome Aggregation Database;
3. ClinGen’s Dosage Sensitivity Map; and
4. ClinGen’s Community Curation Curation Baseline Annotation.

Launched in December 2020, the GenCC DB is a gene-level knowledgebase for claims on the strength of gene disease relationships made by submitters, much like a “ClinVar for genes.” The GenCC comprises organizations that currently provide online resources (e.g. ClinGen, DECIPHER, GEL PanelApp, OMIM, Orphanet, PanelApp Australia, TGMI’s G2P), as well as diagnostic labs that have committed to sharing their internal curated gene-level knowledge (e.g. Ambry, Illumina, Invitae, Myriad Women’s Health, MGB Laboratory for Molecular Medicine).  With data from over 200,000 individuals, gnomAD contains annotations that aid in variant interpretation, including allele frequency, gene expression data, automated and manually curated loss-of-function annotations, constraint scores, heteroplasmy estimates for mitochondrial variation, and structural annotations.

The ClinGen Dosage Sensitivity Map provides evidence-based assessments of haploinsufficiency and triplosensitivity for genes and genomic regions critical for interpreting copy number variants. Users can search by gene or by genomic coordinates, and the data is downloadable for easy incorporation into genomic pipelines. ClinGen’s Baseline Annotation effort improves data transparency through the use of a web-based annotation tool, Hypothes.is, and has the potential to expedite the evaluation of variant pathogenicity, gene-disease validity and more.

The workshop will include an overview of each resource and then lead participants through interactive demonstrations that will teach participants how to use each resource in the context of genomic analysis and interpretation (e.g. for interpreting gene-disease relationships and variant pathogenicity).