Data sharing as a national quality improvement program: reporting on BRCA1 and BRCA2 variant-interpretation comparisons through the Canadian Open Genetics Repository (COGR)

Genet Med. 2018 Mar;20(3):294-302. doi: 10.1038/gim.2017.80. Epub 2017 Jul 20.


PurposeThe purpose of this study was to develop a national program for Canadian diagnostic laboratories to compare DNA-variant interpretations and resolve discordant-variant classifications using the BRCA1 and BRCA2 genes as a case study.MethodsBRCA1 and BRCA2 variant data were uploaded and shared through the Canadian Open Genetics Repository (COGR; A total of 5,554 variant observations were submitted; classification differences were identified and comparison reports were sent to participating laboratories. Each site had the opportunity to reclassify variants. The data were analyzed before and after the comparison report process to track concordant- or discordant-variant classifications by three different models.ResultsVariant-discordance rates varied by classification model: 38.9% of variants were discordant when using a five-tier model, 26.7% with a three-tier model, and 5.0% with a two-tier model. After the comparison report process, the proportion of discordant variants dropped to 30.7% with the five-tier model, to 14.2% with the three-tier model, and to 0.9% using the two-tier model.ConclusionWe present a Canadian interinstitutional quality improvement program for DNA-variant interpretations. Sharing of variant knowledge by clinical diagnostic laboratories will allow clinicians and patients to make more informed decisions and lead to better patient outcomes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Canada
  • Clinical Decision-Making
  • Data Accuracy*
  • Databases, Genetic
  • Genes, BRCA1
  • Genes, BRCA2
  • Genetic Counseling
  • Genetic Testing / methods
  • Genetic Testing / standards*
  • Genetic Variation
  • Government Programs
  • Humans
  • Information Dissemination*
  • Quality Improvement*
  • Reproducibility of Results
  • Workflow