Journal
HUMAN MUTATION
Volume 43, Issue 12, Pages 2054-2062Publisher
WILEY-HINDAWI
DOI: 10.1002/humu.24468
Keywords
ClinVar; genomics; hereditary cancer genes; reanalysis; variant classification
Categories
Funding
- Australian Government Research Training Program (RTP) Scholarship
- Australian National Health and Medical Research Council [1061779, 1161589, 1139071]
- QIMR Berghofer Medical Research Institute
Ask authors/readers for more resources
This study examined how variant classification changes over time using the ClinVar database. The findings suggest that there are significant changes in variant classification between consecutive semi-annual releases, emphasizing the need for regular reassessment of clinical variant interpretations.
The clinical classification of variants may change with new information, however, there is limited guidance on how often significant changes in variant classification occur. We used ClinVar to examine how variant classification changes over time. We developed a custom parser and accessed variant data from ClinVar between January 2015 and July 2021. The ClinVar-assigned aggregate classification of variants in 121 hereditary cancer genes was harmonized across releases to align to the American College of Medical Genetics and Genomics and the Association for Molecular Pathology terms. Aggregate classification categories were grouped as: benign/likely benign (B/LB); likely pathogenic/pathogenic (LP/P); variant of uncertain significance (VUS); conflicting interpretations of pathogenicity (Conflicting); or Other. We profiled changes in aggregate variant classification between consecutive semi-annual ClinVar releases. The proportion of variants that changed aggregate classification between semi-annual ClinVar releases ranged from 0.6% to 6.4%. The most frequent changes were VUS to conflicting, other to LP/P, and B/LB to Conflicting. A limited number of variants changed aggregate classification from LP/P to B/LB, or vice versa. Our analysis indicates need for regular reassessment of clinical variant interpretations. The parser developed for this project will facilitate extraction of relevant interpretation data from ClinVar.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available