Analysis of hereditary cancer gene variant classifications from ClinVar indicates a need for regular reassessment of clinical assertions.

Autor: Davidson AL; QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.; Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia., Kondrashova O; QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia., Leonard C; QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia., Wood S; QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia., Tudini E; QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.; Australian Genomics, Melbourne, Victoria, Australia., Hollway GE; QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia., Pearson JV; QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia., Newell F; QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia., Spurdle AB; QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia., Waddell N; QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.; Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia.
Jazyk: angličtina
Zdroj: Human mutation [Hum Mutat] 2022 Dec; Vol. 43 (12), pp. 2054-2062. Date of Electronic Publication: 2022 Oct 02.
DOI: 10.1002/humu.24468
Abstrakt: 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.
(© 2022 Wiley Periodicals LLC.)
Databáze: MEDLINE
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