An Initial Survey of the Performances of Exome Variant Analysis and Clinical Reporting Among Diagnostic Laboratories in China

Frontiers in Genetics

Jian Wang¹  Yiping Shen³  Kuo Zhang⁴  Dongsheng Han⁴  Jinming Li⁵  Yanxi Han⁵  Guigao Lin⁵ 

[1] Department of Medical Genetics and Molecular Diagnostic Laboratory, Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China;Division of Genetics and Genomics, Boston Children’s Hospital, Boston, MA, United States;Genetic and Metabolic Central Laboratory, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, China;Graduate School, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China;National Center for Clinical Laboratories, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China;

关键词: exome sequencing;    variant analysis;    variant interpretation;    clinical reporting;    laboratory performance;   

DOI  :  10.3389/fgene.2020.582637

来源: DOAJ

【 摘 要 】

Exome sequencing has become an effective diagnostic method for Mendelian disorders. But the quality of services differs widely across laboratories in China, particularly in variant classification, even with the adoption of the ACMG guidelines. As an effort of quality control and improvement for better clinical utilization of exome sequencing, we assessed the exome data analysis and clinical reporting among Chinese laboratories. Five raw datasets of real clinical samples with associated phenotypes were sent to 53 laboratories. The participants independently performed secondary analysis, variant classification, and reporting. The first round of results was used for identifying problems associated with these aspects. Subsequently, we implemented several corrective actions and a training program was designed based on the identified issues. A second round of five datasets were sent to the same participants. We compared the performances in variant interpretation and reporting. A total of 85.7% (42/49) of participants correctly identified all the variants related with phenotype. Many lines of evidence using the ACMG guidelines were incorrectly utilized, which resulted in a large inter-laboratory discrepancy. After training, the evidence usage problems significantly improved, leading to a more consistent outcome. Participants improved their exome data analysis and clinical reporting capability. Targeted training and a deeper understanding of the ACMG guidelines helped to improve the clinical exome sequencing service in terms of consistency and accuracy in variant classification in China.

【 授权许可】

Unknown