Data sharing to improve concordance in variant interpretation across laboratories: results from the Canadian Open Genetics Repository. Issue 6 (19th April 2021)

• Record Type: Journal Article
• Authors: Mighton, Chloe; Smith, Amanda C; Mayers, Justin; Tomaszewski, Robert; Taylor, Sherryl; Hume, Stacey; Agatep, Ron; Spriggs, Elizabeth; Feilotter, Harriet E; Semenuk, Laura; Wong, Henry; Lazo de la Vega, Lorena; Marshall, Christian R; Axford, Michelle M; Silver, Talia; Charames, George S; Di Gioacchino, Vanessa; Watkins, Nicholas; Foulkes, William D; Clavier, Marcos; Hamel, Nancy; Chong, George; Lamont, Ryan E; Parboosingh, Jillian; Karsan, Aly; Bosdet, Ian; Young, Sean S; Tucker, Tracy; Akbari, Mohammad Reza; Speevak, Marsha D; Vaags, Andrea K; Lebo, Matthew S; Lerner-Ellis, Jordan;
• Other Names: author non-byline.; Agatep Ron author non-byline.; Ainsworth Peter author non-byline.; Akbari Mohammad R. author non-byline.; Aronson Melyssa author non-byline.; Basran Raveen author non-byline.; Blavier Andre author non-byline.; Blumenthal Andrea author non-byline.; Bombard Yvonne author non-byline.; Bosdet Ian author non-byline.; Boycott Kym author non-byline.; Brudno Michael author non-byline.; Buckley Kathleen author non-byline.; Campbell Jodi author non-byline.; Campeau Philippe M. author non-byline.; Care Melanie author non-byline.; Carson Nancy author non-byline.; Chang Martin C. author non-byline.; Di Gioacchino Vanessa author non-byline.; Carter Ronald author non-byline.; Charames George author non-byline.; Chitayat David author non-byline.; Chong George author non-byline.; Chouinard Edmond author non-byline.; Chun Kathy author non-byline.; Craddock Kenneth J. author non-byline.; Docking Rod author non-byline.; Eisen Andrea author non-byline.; Faghfoury Hanna author non-byline.; Farrell Sandra author non-byline.; Feilotter Harriet author non-byline.; Fernandez Bridget author non-byline.; Fiume Marc author non-byline.; Forster-Gibson Cynthia author non-byline.; Friedman Jan author non-byline.; Foulkes William author non-byline.; Goodhand Peter author non-byline.; Hegele Robert author non-byline.; Holter Spring author non-byline.; Horsburgh Sheri author non-byline.; Hughes Lauren author non-byline.; Hume Stacey author non-byline.; Jarinova Olga author non-byline.; Junker Anne author non-byline.; Karsan Aly author non-byline.; Khalouei Sam author non-byline.; Kim Raymond H. author non-byline.; Knoll Joan author non-byline.; Kolomietz Elena author non-byline.; Knoppers Bartha author non-byline.; Lamont Ryan author non-byline.; Lebo Matthew author non-byline.; Lerner-Ellis Jordan author non-byline.; Maire Georges author non-byline.; Marshall Christian author non-byline.; McCready Elizabeth author non-byline.; Mitchell Grant author non-byline.; Morel Chantal author non-byline.; Nelson Tanya author non-byline.; Noor Abdul author non-byline.; O'Connor Brian author non-byline.; O'Rielly Darren author non-byline.; Ouellette Francis author non-byline.; Parboosingh Jillian author non-byline.; Pugh Trevor author non-byline.; Racher Hilary author non-byline.; Rehm Heidi author non-byline.; Riddell Christie author non-byline.; Riviere Jean-Baptiste author non-byline.; Rosenblatt David S. author non-byline.; Rouleau Guy author non-byline.; Ruchon Andrea author non-byline.; Sabatini Peter author non-byline.; Sadikovic Bekim author non-byline.; Semotiuk Kara author non-byline.; Scherer Stephen W. author non-byline.; Shuman Cheryl author non-byline.; Silver Josh author non-byline.; Siminovitch Katherine author non-byline.; Solomon-Izsak Lesley author non-byline.; Soucy Jean-Francois author non-byline.; Speevak Marsha author non-byline.; Stavropoulos James author non-byline.; Stein Lincoln author non-byline.; Taylor Sherryl author non-byline.; Terespolsky Deborah author non-byline.; Tomaszewski Robert author non-byline.; Tucker Tracy author non-byline.; Wintle Richard F. author non-byline.; Wong Nora author non-byline.; Wang Marina author non-byline.; Watkins Nicholas author non-byline.; Waye John S. author non-byline.; White Shana author non-byline.; Woods Michael O. author non-byline.; Wyatt Philip author non-byline.; Young Sean author non-byline.; Zakoor Kathleen-Rose author non-byline.;
• Is Part Of: Journal of medical genetics. Volume 59:Issue 6(2022)
• Page Start: 571
• Page End: 578
• Publication Date: 2021-04-19
• Subjects: genetics -- human genetics -- genetic testing; Medical genetics -- Periodicals; 616.042
• DOI: 10.1136/jmedgenet-2021-107738
• Languages: English
• ISSNs: 1468-6244

Abstract

Abstract : Background: This 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. Methods: Laboratories 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. Results: Twelve 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. Conclusions: The 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.