METHODS: Genomic DNA was analysed using Sanger sequencing and next-generation sequencing (NGS). The Data was evaluated using various databases and in silico prediction tools and classified according to current ACMG standards by two independent experts.
RESULTS: We identified 53 VUS in 30 genes, of which 17 variants (32%) were reclassified. 13% each were downgraded to likely benign (LB) and benign (B) and 6% were upgraded to likely pathogenic (LP). Reclassifications mainly occurred among variants initially classified in 2017-2019, with rates ranging from 50 to 60%.
CONCLUSIONS: The results support the assumption that regular reclassification of VUS is important, as it provides new insights for genetic diagnostics, that benefit patients and guide therapeutic approach.
方法:使用Sanger测序和下一代测序(NGS)分析基因组DNA。使用各种数据库和计算机预测工具对数据进行评估,并由两名独立专家根据当前的ACMG标准进行分类。
结果:我们在30个基因中鉴定出53个VUS,其中17个变异体(32%)被重新分类。分别有13%被降级为可能的良性(LB)和良性(B),6%被升级为可能的致病性(LP)。重新分类主要发生在2017-2019年最初分类的变体中,比率从50%到60%不等。
结论:结果支持常规VUS重新分类很重要的假设,因为它为基因诊断提供了新的见解,使患者受益并指导治疗方法。