Guidance and Consensus
Standards for the interpretation of constitutional copy number gain: Recommendation from the American College of Medical Genetics and Genomics (ACMG) and Clinical Genome Resource (ClinGen)
Chen Xiaoli, Shangguan Shaofang, Xie Hua, Liu Haoran, Liu Weiqiang, An Yu, Shen Yiping
Published 2022-01-10
Cite as Chin J Med Genet, 2022, 39(1): 1-10. DOI: 10.3760/cma.j.cn511374-20200220-00143
Abstract
Copy number variants (CNVs) are common causes of human genetic diseases. CNVs detection has become a routine component of genetic testing, especially for pediatric neurodevelopmental disorders, multiple congenital abnormalities, prenatal evaluation of fetuses with structural anomalies detected by ultrasound. Although the technologies for CNVs detection are continuously improving, the interpretation is still challenging, with significant discordance across different laboratories. In 2020, the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen) developed a guideline for the interpreting and reporting of constitutional copy number variants, which introduced a quantitative, evidence-based scoring framework. Here, we detailed the key points of interpreting the copy number gain based on the guideline, used six examples of different categories to illuminate the scoring process and principles. We encourage a professional understanding and application of this guideline for the detected copy number gains in China in order to further improve the clinical evaluation accuracy and consistency across different laboratories.
Key words:
Constitutional copy number gain; Standards for the interpretation; American College of Medical Genetics and Genomics; Clinical Genome Resource
Contributor Information
Chen Xiaoli
Department of Genetics, Capital Institute of Pediatrics, Beijing 100020, China
Shangguan Shaofang
Department of Genetics, Capital Institute of Pediatrics, Beijing 100020, China
Xie Hua
Department of Genetics, Capital Institute of Pediatrics, Beijing 100020, China
Liu Haoran
Department of Genetics, Capital Institute of Pediatrics, Beijing 100020, China
Liu Weiqiang
Key Laboratory of Major Obstetric Diseases, the Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510150, China
An Yu
Institute of Human Phenome, Fudan University, Shanghai 200433, China
Shen Yiping
Central Laboratory of Genetic and Metabolic Disease, Guangxi Maternal and Child Health Care Hospital, Nanning, Guangxi 530005, China
Department of Medical Genetics, Shanghai Children’s Medical Center, Shanghai 200127, China
Department of Genetics and Genomics, Boston Children’s Hospital, MA 02115, USA
