A large-scale retrospective analysis of copy number variations in single center using ACMG-ClinGen latest guidelines.
10.3760/cma.j.cn511374-20210519-00429
- VernacularTitle:采用ACMG－ClinGen新指南对单中心拷贝数变异的大样本进行回顾性分析
- Author:
Yuxin ZHANG
1
;
Jiangyang XUE
;
Lulu YAN
;
Yingwen LIU
;
Danyan ZHUANG
;
Min XIE
;
Yibo CHEN
;
Yu AN
;
Yiping SHEN
;
Haibo LI
Author Information
1. Comprehensive Prevention and Treatment Center for Birth Defects, Ningbo Women and Children's Hospital, Ningbo, Zhejiang 315000, China. lihaibo-775@163.com.
- Publication Type:Journal Article
- MeSH:
DNA Copy Number Variations;
Genetic Testing;
Genetic Variation;
Genome, Human;
Humans;
Mutation;
Retrospective Studies
- From:
Chinese Journal of Medical Genetics
2022;39(8):814-818
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE: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.
METHODS: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.
RESULTS: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.
CONCLUSION: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.
