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Data sharing to improve concordance in variant interpretation across laboratories: results from the Canadian Open
Chloe Mighton1,2,3,4, Amanda C Smith5, Justin Mayers2
1Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada.
Journal of Medical Genetics
|April 20, 2021
Summary
The Canadian Open Genetics Repository (COGR) successfully reduced discordant genetic variant interpretations among clinical laboratories. This collaborative platform enhances the accuracy and reliability of genetic testing results.
Area of Science:
- Clinical Molecular Genetics
- Bioinformatics
- Genomic Data Sharing
Background:
- Discordant variant interpretations pose challenges in clinical molecular genetics.
- Standardized approaches are needed to ensure accurate genetic testing results.
Purpose of the Study:
- To identify and resolve conflicting genetic variant interpretations across clinical laboratories.
- To evaluate the effectiveness of the Canadian Open Genetics Repository (COGR) in harmonizing variant classifications.
Main Methods:
- Laboratories uploaded variant data to the Franklin Genoox platform for analysis.
- Discordant classifications were identified and laboratories reassessed variants.
- Variant classifications were analyzed using five-tier, three-tier, and two-tier models.
- Automated classifications from Franklin were compared against COGR classifications.
Main Results:
- Out of 44,510 unique variants, 2419 (5.4%) were classified by multiple laboratories.
- Discordant variants decreased significantly after reassessment across all classification models.
- The two-tier model showed the most substantial reduction in discordance, from 3.2% to 1.5%.
- Automated Franklin classifications demonstrated high sensitivity (94.5%) and specificity (96.6%) for actionable variants.
Conclusions:
- The COGR offers a standardized method for identifying and reducing discordant variant interpretations.
- Quality assurance programs like COGR are crucial for the widespread clinical implementation of genetic testing.
- Collaborative efforts improve the consistency and reliability of genetic test results.