Data sharing to improve concordance in variant interpretation across laboratories: results from the Canadian Open Genetics Repository
| Autor: | Michelle M. Axford, Ron Agatep, Marcos Clavier, Stacey Hume, Elizabeth Spriggs, Andrea K Vaags, George S. Charames, Harriet Feilotter, Nicholas A. Watkins, Amanda C. Smith, Tracy Tucker, Matthew S. Lebo, Vanessa Di Gioacchino, Jordan Lerner-Ellis, Ian Bosdet, Mohammad R. Akbari, William D. Foulkes, Chloe Mighton, Sean S. Young, Lorena Lazo de la Vega, Talia Silver, Ryan E. Lamont, Laura Semenuk, Robert Tomaszewski, Christian R. Marshall, Nancy Hamel, Justin Mayers, Henry K. Wong, Jillian S. Parboosingh, Marsha Speevak, Aly Karsan, George Chong, Sherryl Taylor |
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| Rok vydání: | 2021 |
| Předmět: |
Canada
Concordance Article 03 medical and health sciences Likely benign Genetics medicine Humans Genetic Predisposition to Disease Genetic Testing Clinical care Uncertain significance Genetics (clinical) Likely pathogenic 030304 developmental biology Genetic testing 0303 health sciences medicine.diagnostic_test Information Dissemination business.industry 030305 genetics & heredity Genetic Variation Human genetics Data sharing Laboratories business |
| Zdroj: | J Med Genet |
| ISSN: | 1468-6244 0022-2593 |
| DOI: | 10.1136/jmedgenet-2021-107738 |
| Popis: | BackgroundThis study aimed to identify and resolve discordant variant interpretations across clinical molecular genetic laboratories through the Canadian Open Genetics Repository (COGR), an online collaborative effort for variant sharing and interpretation.MethodsLaboratories uploaded variant data to the Franklin Genoox platform. Reports were issued to each laboratory, summarising variants where conflicting classifications with another laboratory were noted. Laboratories could then reassess variants to resolve discordances. Discordance was calculated using a five-tier model (pathogenic (P), likely pathogenic (LP), variant of uncertain significance (VUS), likely benign (LB), benign (B)), a three-tier model (LP/P are positive, VUS are inconclusive, LB/B are negative) and a two-tier model (LP/P are clinically actionable, VUS/LB/B are not). We compared the COGR classifications to automated classifications generated by Franklin.ResultsTwelve laboratories submitted classifications for 44 510 unique variants. 2419 variants (5.4%) were classified by two or more laboratories. From baseline to after reassessment, the number of discordant variants decreased from 833 (34.4% of variants reported by two or more laboratories) to 723 (29.9%) based on the five-tier model, 403 (16.7%) to 279 (11.5%) based on the three-tier model and 77 (3.2%) to 37 (1.5%) based on the two-tier model. Compared with the COGR classification, the automated Franklin classifications had 94.5% sensitivity and 96.6% specificity for identifying actionable (P or LP) variants.ConclusionsThe COGR provides a standardised mechanism for laboratories to identify discordant variant interpretations and reduce discordance in genetic test result delivery. Such quality assurance programmes are important as genetic testing is implemented more widely in clinical care. |
| Databáze: | OpenAIRE |
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