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

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 5...

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Autores principales: Harrison, Steven M., Austin‐Tse, Christina A., Kim, Serra, Lebo, Matthew, Leon, Annette, Murdock, David, Radhakrishnan, Aparna, Shirts, Brian H., Steeves, Marcie, Venner, Eric, Gibbs, Richard A., Jarvik, Gail P., Rehm, Heidi L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9206690/
https://www.ncbi.nlm.nih.gov/pubmed/34923710
http://dx.doi.org/10.1002/humu.24317
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author Harrison, Steven M.
Austin‐Tse, Christina A.
Kim, Serra
Lebo, Matthew
Leon, Annette
Murdock, David
Radhakrishnan, Aparna
Shirts, Brian H.
Steeves, Marcie
Venner, Eric
Gibbs, Richard A.
Jarvik, Gail P.
Rehm, Heidi L.
author_facet Harrison, Steven M.
Austin‐Tse, Christina A.
Kim, Serra
Lebo, Matthew
Leon, Annette
Murdock, David
Radhakrishnan, Aparna
Shirts, Brian H.
Steeves, Marcie
Venner, Eric
Gibbs, Richard A.
Jarvik, Gail P.
Rehm, Heidi L.
author_sort Harrison, Steven M.
collection PubMed
description 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.
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spelling pubmed-92066902022-10-14 Harmonizing variant classification for return of results in the All of Us Research Program Harrison, Steven M. Austin‐Tse, Christina A. Kim, Serra Lebo, Matthew Leon, Annette Murdock, David Radhakrishnan, Aparna Shirts, Brian H. Steeves, Marcie Venner, Eric Gibbs, Richard A. Jarvik, Gail P. Rehm, Heidi L. Hum Mutat Research Articles 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. John Wiley and Sons Inc. 2021-12-28 2022-08 /pmc/articles/PMC9206690/ /pubmed/34923710 http://dx.doi.org/10.1002/humu.24317 Text en © 2021 The Authors. Human Mutation published by Wiley Periodicals LLC. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Articles
Harrison, Steven M.
Austin‐Tse, Christina A.
Kim, Serra
Lebo, Matthew
Leon, Annette
Murdock, David
Radhakrishnan, Aparna
Shirts, Brian H.
Steeves, Marcie
Venner, Eric
Gibbs, Richard A.
Jarvik, Gail P.
Rehm, Heidi L.
Harmonizing variant classification for return of results in the All of Us Research Program
title Harmonizing variant classification for return of results in the All of Us Research Program
title_full Harmonizing variant classification for return of results in the All of Us Research Program
title_fullStr Harmonizing variant classification for return of results in the All of Us Research Program
title_full_unstemmed Harmonizing variant classification for return of results in the All of Us Research Program
title_short Harmonizing variant classification for return of results in the All of Us Research Program
title_sort harmonizing variant classification for return of results in the all of us research program
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9206690/
https://www.ncbi.nlm.nih.gov/pubmed/34923710
http://dx.doi.org/10.1002/humu.24317
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