Harmonizing variant classification for return of results in the All of Us Research Program.

TitleHarmonizing variant classification for return of results in the All of Us Research Program.
Publication TypeJournal Article
Year of Publication2022
AuthorsHarrison, SM, Austin-Tse, CA, Kim, S, Lebo, M, Leon, A, Murdock, DR, Radhakrishnan, A, Shirts, BH, Steeves, M, Venner, E, Gibbs, RA, Jarvik, GP, Rehm, HL
JournalHum Mutat
Date Published2022 Aug
KeywordsGenetic Testing, Genetic Variation, Genome, Human, Genomics, Humans, Population Health, United States

The All of Us Research Program (AoURP) is a historic effort to accelerate research and improve healthcare by generating and collating data from one million people in the United States. Participants will have the option to receive results from their genome analysis, including actionable findings in 59 gene-disorder pairs for which disorder-associated variants are recommended for return by the American College of Medical Genetics and Genomics. To ensure consistent reporting across the AoURP, in a prelaunch study the four participating clinical laboratories shared all variant classifications in the 59 genes of interest from their internal databases. Of the 11,813 unique variants classified by at least two of the four laboratories, classifications were concordant with regard to reportability for 99.1% (11,711), with only 0.9% (102) having reportability differences. Through variant reassessment, data sharing, and discussion of rationale, participating laboratories resolved all 102 reportable differences. These approaches will be maintained during routine AoU reporting to ensure continuous classification harmonization and consistent reporting within AoURP.

Alternate JournalHum Mutat
PubMed ID34923710
PubMed Central IDPMC9206690
Grant ListOT2 OD002750 / OD / NIH HHS / United States
OT2 OD002751 / OD / NIH HHS / United States
OT2 OD002748 / OD / NIH HHS / United States

Similar Publications