RT Journal Article
SR Electronic
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
FD BMJ Publishing Group Ltd
SP 571
OP 578
DO 10.1136/jmedgenet-2021-107738
VO 59
IS 6
A1 Mighton, Chloe
A1 Smith, Amanda C
A1 Mayers, Justin
A1 Tomaszewski, Robert
A1 Taylor, Sherryl
A1 Hume, Stacey
A1 Agatep, Ron
A1 Spriggs, Elizabeth
A1 Feilotter, Harriet E
A1 Semenuk, Laura
A1 Wong, Henry
A1 Lazo de la Vega, Lorena
A1 Marshall, Christian R
A1 Axford, Michelle M
A1 Silver, Talia
A1 Charames, George S
A1 Di Gioacchino, Vanessa
A1 Watkins, Nicholas
A1 Foulkes, William D
A1 Clavier, Marcos
A1 Hamel, Nancy
A1 Chong, George
A1 Lamont, Ryan E
A1 Parboosingh, Jillian
A1 Karsan, Aly
A1 Bosdet, Ian
A1 Young, Sean S
A1 Tucker, Tracy
A1 Akbari, Mohammad Reza
A1 Speevak, Marsha D
A1 Vaags, Andrea K
A1 Lebo, Matthew S
A1 Lerner-Ellis, Jordan
A1 ,
YR 2022
UL http://jmg.bmj.com/content/59/6/571.abstract
AB 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.