GHGA Lecture Series: Marina DiStefano (virtual)

Marina DiStefano from the Broad Instiute will present "The Gene Curation Coalition: A Global Effort to Harmonize Gene-Disease Evidence Resources" at the GHGA lecture series ("Advances in Data-Driven Biomedicine") on January 18, 2022.

Watch this lecture here.


The Gene Curation Coalition (GenCC) was formed in 2017 to bring together international resources reporting the validity of gene-disease relationships. It comprises organizations that provide online gene-level resources as well as diagnostic laboratories that have committed to sharing their internally curated gene-level knowledge. We used a Delphi method to survey members of both the GenCC and the broader international genetics community to harmonize terms to describe gene-disease validity. Based on 312 responses from three rounds of surveys, “Definitive, Strong, Moderate, Limited, Disputed Evidence, Refuted Evidence, Animal Model Only, and No Known Disease Relationship” were the agreed terms. Next, the GenCC developed a unified database to display curated gene-disease validity assertions from its members and in December 2020, the beta version was launched ( Each entry is an assertion for a gene, a disease, and a mode of inheritance, including publicly available evidence supporting that assertion. Different displays within the database show assertions by submitter, by disease, by gene, and by clinical validity level. All assertions are mapped to the standardized gene-disease validity terms generated by the Delphi survey. Disease terms are standardized by mapping all submitted disease terms to the Monarch Disease Ontology (MONDO). Currently, the database contains 16338 gene-disease assertions on 4656 unique genes submitted by 12 different groups. The GenCC is using these data to identify and resolve classification discrepancies. Future plans include user-specific search parameters and a panel builder function that allows searching by keyword, Human Phenotype Ontology terms, or any disease term present in a MONDO hierarchy to generate a filterable gene list. The list can then be downloaded and used to inform clinical testing panel design or indication-based analysis during exome or genome sequencing. This effort will help to harmonize gene-disease validity across clinical and research curation efforts.


Marina DiStefano PhD, FACMG  is a board-certified clinical molecular geneticist and is an Associate Laboratory Director at the Clinical Research Sequencing Platform at the Broad Institute. She also directs the ClinGen Biocuration core based at Broad and sits as a framework expert on 15 ClinGen expert panels. Her research interests involve testing and setting curation standards in gene curation, variant curation, and disease ontologies. She is one of the founders and current Steering Committee Co-Chairs of the Gene Curation Coalition (GenCC).