High-quality interpretation of BRCA1/2 variants plays a critical role in the clinical practice of precision medicine. However, a comprehensive system to evaluate the quality and accuracy of variant interpretation has yet to be established. This study investigates the performance of an interpretation system in evaluating the capacities of BRCA1/2 interpretation among distinct laboratories in China. The evaluation system is based on a reference database that contains 750 different variants in BRCA1/2. Evaluation was performed among 41 laboratories in China. We classified their performance into five levels. Only level A was considered qualified. This level allows for a 0.3% error rate for clinical decision-related misinterpretation; 26 of 41 laboratories (63%) met the qualified standard, while 7 laboratories were at levels D and E, which indicated egregious mistakes and systemic problems in variant interpretation. Due to strict quality demands, the interpretation of several variants was amended, which largely influenced the quality rate. The number of qualified laboratories would decrease from 26 to 17 if those incorrect recommended interpretations were not corrected. This evaluation system provides a potential approach for standardisation of variant interpretation and lowers the discordance of variant interpretation between different laboratories. A well-designed interpretation ability evaluation is essential to evaluate the interpretation level of laboratories before they provide service in real-world clinical settings.
- genetic predisposition to disease
- genetic counseling
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KS, RW and SQ contributed equally.
Contributors Conception and direction: JH, FC, XC, XY, SZ. Set the rules and organised the evaluation: RW, SQ, WZ, TY. Rating of evaluation results: BC, KS. Recommended variant classification and reviewed controversial variants: PD, AZ, JZ, JW. Manuscript writing: KS. Manuscript review and editing: KW, LW.
Funding This work was supported by grants from the National Key Research and Development Program of China (2018YFC1002402, 2016YFC1000301 and 2017YFC1309103), GRF Grants CityU 11206120, CityU 11210119 and NSFC 61972329, and the Science, Technology and Innovation Commission of Shenzhen Municipality Grant No. GJHZ20170314152701465. This work was supported by China National GeneBank (CNGB).
Competing interests All the laboratories involved in this research were confidential. Each laboratory could only receive their own test results. Some authors are from the laboratories participating in this evaluation. However, they will not benefit from the publication of this research.
Patient consent for publication Not required.
Ethics approval This research study was approved by the institutional review board on bioethics and biosafety of BGI IRB.
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement All data relevant to the study are included in the article or uploaded as supplementary information.
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