Germline variants of BRCA1/2 gene with uncertain significance:a reappraisal
10.13315/j.cnki.cjcep.2024.10.007
- VernacularTitle:BRCA1/2基因胚系变异意义未明位点的重新分析
- Author:
Jianfei FANG
1
,
2
;
Zhengxiao MA
;
Rui ZHU
;
Dan SU
Author Information
1. 浙江省肿瘤医院病理科,杭州 310022
2. 中国科学院杭州医学研究所,杭州 310022
- Keywords:
BRCA1/2 gene;
germline variation;
variants of un-certain significance
- From:
Chinese Journal of Clinical and Experimental Pathology
2024;40(10):1041-1045
- CountryChina
- Language:Chinese
-
Abstract:
Purpose BRCA1/2 gene germline variants of the uncertain significance(VUS)are categorized into five clas-ses based on their risk levels,and three classes require regular periodic analysis due to their unclear clinical significance.The aim of this study was to investigate the influence of updating var-iation evidences on the VUS sites and guide clinical diagnosis and treatment.Methods The VUS sites in BRCA1/2 gene were analyzed.971 samples(breast or ovarian cancer)that un-derwent BRCA1/2 germline testing were stored.The VUS sites in BRCA1/2 gene were further reinterpreted by integrating the following evidences,including population frequency database,disease database,computer software prediction,co-segregation evidence,allelic evidence and population cohort evidence to determine whether the variation classification was changed.Results The number of the patients with VUS sites was 142,accounting for 14.6％(142/971).The total number of VUS sites was 128,among which the proportions of missense muta-tion,synonymous mutation,in-frame non-shifted mutation and non-coding region mutation were 70.3％,4.7％,3.1％and 21.9％,respectively.Reinterpretation of VUS sites discovered that 11.7％(15/128)of VUS sites could be downgraded to Class 2,likely benign.Conclusion With the continuous in-creasing evidences of germline variation,the variation classifica-tion of VUS sites will be changed after periodic analysis.
