Tracking updates in clinical databases increases efficiency for variant reanalysis.

PURPOSE

Variant interpretation, guided by American College of Medical Genetics and Genomics guidelines, can inform clinical decision-making. However, interpretations may change over time for a variety of reasons. Periodic reanalysis of previous variant interpretations is important to ensure that reported genetic findings remain accurate according to current knowledge.

METHODS

We performed automated filtering by comparing ClinVar variants available in August 2020 with those from August 2021 to screen for potential reanalysis candidates from 3 projects. These variants were subsequently interpreted based on the American College of Medical Genetics and Genomics/Association for Molecular Pathology variant interpretation guideline or ClinGen revised gene-specific guidelines if applicable.

RESULTS

Our method annotated 241 unique variants requiring reanalysis, from 3 projects containing 3,832,210 previously interpreted variants, including those filtered automatically. Among these 241 variants, 43 variants changed interpretation, including 55.81% ( = 24) with upgraded and 44.19% ( = 19) with downgraded classifications. An efficiency study showed that our strategy increased the reanalysis efficiency and saved reviewing time.

CONCLUSION

We demonstrated an effective high-throughput method, initiating from external data updates, to achieve variant reanalysis in a clinical laboratory. This filtering method reduced the number of variants that need to be reanalyzed, screened potential variants, and saved time and cost for clinical laboratories.