ABSTRACT
Purpose
Several groups and resources provide information that pertains to the validity of
gene–disease relationships used in genomic medicine and research; however, universal
standards and terminologies to define the evidence base for the role of a gene in
disease and a single harmonized resource were lacking. To tackle this issue, the Gene
Curation Coalition (GenCC) was formed.
Methods
The GenCC drafted harmonized definitions for differing levels of gene–disease validity
on the basis of existing resources, and performed a modified Delphi survey with 3
rounds to narrow the list of terms. The GenCC also developed a unified database to
display curated gene–disease validity assertions from its members.
Results
On the basis of 241 survey responses from the genetics community, a consensus term
set was chosen for grading gene–disease validity and database submissions. As of December
2021, the database contained 15,241 gene–disease assertions on 4569 unique genes from
12 submitters. When comparing submissions to the database from distinct sources, conflicts
in assertions of gene–disease validity ranged from 5.3% to 13.4%.
Conclusion
Terminology standardization, sharing of gene–disease validity classifications, and
resolution of curation conflicts will facilitate collaborations across international
curation efforts and in turn, improve consistency in genetic testing and variant interpretation.
Keywords
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Article info
Publication history
Published online: May 04, 2022
Accepted:
April 7,
2022
Received in revised form:
April 6,
2022
Received:
December 30,
2021
Identification
Copyright
© 2022 by American College of Medical Genetics and Genomics. Published by Elsevier Inc.
