TY - JOUR T1 - Data sharing to improve concordance in variant interpretation across laboratories: results from the Canadian Open Genetics Repository JF - Journal of Medical Genetics JO - J Med Genet SP - 571 LP - 578 DO - 10.1136/jmedgenet-2021-107738 VL - 59 IS - 6 AU - Chloe Mighton AU - Amanda C Smith AU - Justin Mayers AU - Robert Tomaszewski AU - Sherryl Taylor AU - Stacey Hume AU - Ron Agatep AU - Elizabeth Spriggs AU - Harriet E Feilotter AU - Laura Semenuk AU - Henry Wong AU - Lorena Lazo de la Vega AU - Christian R Marshall AU - Michelle M Axford AU - Talia Silver AU - George S Charames AU - Vanessa Di Gioacchino AU - Nicholas Watkins AU - William D Foulkes AU - Marcos Clavier AU - Nancy Hamel AU - George Chong AU - Ryan E Lamont AU - Jillian Parboosingh AU - Aly Karsan AU - Ian Bosdet AU - Sean S Young AU - Tracy Tucker AU - Mohammad Reza Akbari AU - Marsha D Speevak AU - Andrea K Vaags AU - Matthew S Lebo AU - Jordan Lerner-Ellis A2 - , Y1 - 2022/06/01 UR - http://jmg.bmj.com/content/59/6/571.abstract N2 - 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.All data relevant to the study are included in the article or uploaded as supplementary information. ER -