1. The Gene Curation Coalition: A global effort to harmonize gene-disease evidence resources.
- Author
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DiStefano, MT, Goehringer, S, Babb, L, Alkuraya, FS, Amberger, J, Amin, M, Austin-Tse, C, Balzotti, M, Berg, JS, Birney, E, Bocchini, C, Bruford, EA, Coffey, AJ, Collins, H, Cunningham, F, Daugherty, LC, Einhorn, Y, Firth, HV, Fitzpatrick, DR, Foulger, RE, Goldstein, J, Hamosh, A, Hurles, MR, Leigh, SE, Leong, IUS, Maddirevula, S, Martin, CL, McDonagh, EM, Olry, A, Puzriakova, A, Radtke, K, Ramos, EM, Rath, A, Riggs, ER, Roberts, AM, Rodwell, C, Snow, C, Stark, Z, Tahiliani, J, Tweedie, S, Ware, JS, Weller, P, Williams, E, Wright, CF, Yates, TM, Rehm, HL, DiStefano, MT, Goehringer, S, Babb, L, Alkuraya, FS, Amberger, J, Amin, M, Austin-Tse, C, Balzotti, M, Berg, JS, Birney, E, Bocchini, C, Bruford, EA, Coffey, AJ, Collins, H, Cunningham, F, Daugherty, LC, Einhorn, Y, Firth, HV, Fitzpatrick, DR, Foulger, RE, Goldstein, J, Hamosh, A, Hurles, MR, Leigh, SE, Leong, IUS, Maddirevula, S, Martin, CL, McDonagh, EM, Olry, A, Puzriakova, A, Radtke, K, Ramos, EM, Rath, A, Riggs, ER, Roberts, AM, Rodwell, C, Snow, C, Stark, Z, Tahiliani, J, Tweedie, S, Ware, JS, Weller, P, Williams, E, Wright, CF, Yates, TM, and Rehm, HL
- 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.
- Published
- 2022