Tracking Updates in Clinical Databases Increases Efficiency for Variant Reanalysis

Authors

Lele Li
Xia Tian
Vaughan Woodzell
Richard A Gibbs
Bo Yuan
Eric Venner

Publication Date

1-1-2024

Journal

Genetics in Medicine Open

DOI

10.1016/j.gimo.2024.101841

PMID

39669589

PMCID

PMC11613846

PubMedCentral® Posted Date

5-19-2024

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

Keywords

ACMG guideline, ClinVar, Efficiency, Reanalysis, Screening

Abstract

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% (

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.