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. 2022 Aug;24(8):1732-1742.
doi: 10.1016/j.gim.2022.04.017. Epub 2022 May 4.

The Gene Curation Coalition: A global effort to harmonize gene-disease evidence resources

Marina T DiStefano  1 , Scott Goehringer  2 , Lawrence Babb  3 , Fowzan S Alkuraya  4 , Joanna Amberger  5 , Mutaz Amin  6 , Christina Austin-Tse  7 , Marie Balzotti  8 , Jonathan S Berg  9 , Ewan Birney  10 , Carol Bocchini  5 , Elspeth A Bruford  11 , Alison J Coffey  12 , Heather Collins  13 , Fiona Cunningham  14 , Louise C Daugherty  15 , Yaron Einhorn  16 , Helen V Firth  17 , David R Fitzpatrick  18 , Rebecca E Foulger  19 , Jennifer Goldstein  9 , Ada Hamosh  5 , Matthew R Hurles  20 , Sarah E Leigh  21 , Ivone U S Leong  21 , Sateesh Maddirevula  4 , Christa L Martin  2 , Ellen M McDonagh  22 , Annie Olry  6 , Arina Puzriakova  21 , Kelly Radtke  23 , Erin M Ramos  24 , Ana Rath  6 , Erin Rooney Riggs  25 , Angharad M Roberts  26 , Charlotte Rodwell  6 , Catherine Snow  21 , Zornitza Stark  27 , Jackie Tahiliani  28 , Susan Tweedie  29 , James S Ware  30 , Phillip Weller  25 , Eleanor Williams  21 , Caroline F Wright  31 , Thabo Michael Yates  18 , Heidi L Rehm  32
Affiliations

The Gene Curation Coalition: A global effort to harmonize gene-disease evidence resources

Marina T DiStefano et al. Genet Med. 2022 Aug.

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: Database; GenCC; Gene curation; Genetic diagnosis; The Gene Curation Coalition.

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Conflict of interest statement

Conflict of Interest R.E.F. is an employee of SciBite Ltd, an Elsevier company. Her work toward this paper was performed when she was employed by Genomics England. The following authors are employees for a commercial laboratory that offers clinical genetic testing: M.B., A.J.C., K.R., J.T. All other authors declare no conflicts of interest.

Figures

Figure 1
Figure 1. Phases of the modified Delphi survey process for GenCC gene-disease validity terminology.
Figure 2
Figure 2. Summary statistics for the GenCC database
A) Map of users by country with the top 7 countries listed as of 9/14/21. B) A summary of all data submitted to the GenCC database as of 12/21 including a breakdown of gene-disease validity claims. C) A graph of the number of submissions per gene (N=4569 genes, average is 2 submissions)
Figure 3
Figure 3. Screenshots of the GenCC database
A) the landing page; B) the gene level page sorted by classification C) Submission-specific page for an entry; D) Submitter page
See this image and copyright information in PMC

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