Zhang Yuxin, Xue Jiangyang, Yan Lulu, Liu Yingwen, Zhuang Danyan, Xie Min, Chen Yibo, An Yu, Shen Yiping, Li Haibo
Comprehensive Prevention and Treatment Center for Birth Defects, Ningbo Women and Children's Hospital, Ningbo, Zhejiang 315000, China.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2022 Aug 10;39(8):814-818. doi: 10.3760/cma.j.cn511374-20210519-00429.
Through a retrospective large sample analysis of copy number variants in single center, we explored the technical standards for the interpretation and reporting of constitutional copy-number variants (CNVs) jointly proposed by the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen) in 2019, analyzing its impact on CNVs ratings and the improvement in the consistency of the classification of CNVs in clinical laboratories.
236 CNVs that assessed as pathogenic, uncertain significant (including likely pathogenic, uncertain and likely benign) by the 2011 ACMG guidelines between August 2018 and December 2019 in our center were re-analyzed. Four working group members of the center reclassified and evaluated 235 CNVs according to 2019 ACMG guidelines.
The consistency of clinical significance classification of CNVs was 91% and the α test coefficient was 0.98 among four working group members. Compared with the 2011 and 2019 ACMG technical standards for the CNVs classification, evaluation of pathogenicity and uncertain significant is basically consistent. 90% (45/50) of likely pathogenic and likely benign CNVs were Re-evaluated as variants of uncertain significance, and the difference is significant.
The new version ACMG/ClinGen guidelines for the evaluation of CNVs developed semi-quantitative point-based scoring system and help to improve the consistency in clinical classifications. It can also make the interpretation of CNVs more standardized and transparent.
通过单中心拷贝数变异的回顾性大样本分析，探讨美国医学遗传学与基因组学学会（ACMG）和临床基因组资源（ClinGen）于2019年联合提出的关于结构拷贝数变异（CNV）解读与报告的技术标准，分析其对CNV评级的影响以及临床实验室中CNV分类一致性的改善情况。
对2018年8月至2019年12月期间在本中心按照2011年ACMG指南评估为致病性、意义不明确（包括可能致病性、意义不明确和可能良性）的236个CNV进行重新分析。中心的四名工作组成员根据2019年ACMG指南对235个CNV进行重新分类和评估。
四名工作组成员之间CNV临床意义分类的一致性为91%，α检验系数为0.98。与2011年和2019年ACMG的CNV分类技术标准相比，致病性和意义不明确的评估基本一致。90%（45/50）的可能致病性和可能良性的CNV被重新评估为意义不明确的变异，差异具有统计学意义。
新版ACMG/ClinGen的CNV评估指南制定了基于半定量点的评分系统，有助于提高临床分类的一致性，还能使CNV的解读更加标准化和透明。
