Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen)
Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen)
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DOI：
10.1038/s41436-019-0686-8
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发表时间：
2020-02-01
影响因子：
8.8
通讯作者：
Martin, Christa Lese
中科院分区：
文献类型：
--
作者：
Riggs, Erin Rooney;Andersen, Erica F.;Martin, Christa Lese
目的拷贝数分析检测整个基因组的致病性丢失和获得，建议用于评估神经发育障碍和/或多重先天性异常的个体，以及超声异常的胎儿。在这十年中，这种分析已在临床上广泛使用，在理解拷贝数变异（CNVs）在受影响的个人和一般人群中的影响方面取得了巨大的进步。然而，阵列和下一代测序技术的持续广泛应用将扩大临床环境中遇到的CNV类型，以及我们对它们对人类健康影响的理解。方法为了帮助临床实验室对CNV进行分类和报告，无论用于识别它们的技术如何，美国医学遗传学和基因组学学院与美国国立卫生研究院（NIH）资助的临床基因组资源（ClinGen）项目合作制定了以下专业标准。本次更新引入了一个定量的、基于证据的评分框架;鼓励实施广泛用于序列变异分类的五层分类系统;并建议将变异的基于证据的分类与其对特定个体的潜在影响“脱钩”。结论这些专业标准将指导体质CNVs的评价，并鼓励临床实验室之间的一致性和透明度。
Purpose Copy-number analysis to detect disease-causing losses and gains across the genome is recommended for the evaluation of individuals with neurodevelopmental disorders and/or multiple congenital anomalies, as well as for fetuses with ultrasound abnormalities. In the decade that this analysis has been in widespread clinical use, tremendous strides have been made in understanding the effects of copy-number variants (CNVs) in both affected individuals and the general population. However, continued broad implementation of array and next-generation sequencing-based technologies will expand the types of CNVs encountered in the clinical setting, as well as our understanding of their impact on human health. Methods To assist clinical laboratories in the classification and reporting of CNVs, irrespective of the technology used to identify them, the American College of Medical Genetics and Genomics has developed the following professional standards in collaboration with the National Institutes of Health (NIH)-funded Clinical Genome Resource (ClinGen) project. Results This update introduces a quantitative, evidence-based scoring framework; encourages the implementation of the five-tier classification system widely used in sequence variant classification; and recommends "uncoupling" the evidence-based classification of a variant from its potential implications for a particular individual. Conclusion These professional standards will guide the evaluation of constitutional CNVs and encourage consistency and transparency across clinical laboratories.