Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.
Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.
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DOI：
10.1038/gim.2015.30
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发表时间：
2015-05
期刊：
影响因子：
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通讯作者：
ACMG Laboratory Quality Assurance Committee
中科院分区：
文献类型：
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作者：
Richards S;Aziz N;Bale S;Bick D;Das S;Gastier-Foster J;Grody WW;Hegde M;Lyon E;Spector E;Voelkerding K;Rehm HL;ACMG Laboratory Quality Assurance Committee
美国医学遗传学与基因组学学院 (ACMG) 此前制定了序列变异解释指南。在过去的十年中，随着高通量下一代测序的出现，测序技术迅速发展。通过采用和利用下一代测序，临床实验室现在正在执行越来越多的基因测试，涵盖基因分型、单基因、基因组、外显子组、基因组、转录组和遗传性疾病的表观遗传测定。由于复杂性的增加，基因检测的范式转变伴随着序列解释的新挑战。在此背景下，ACMG于2013年召集了一个由ACMG、分子病理学协会（AMP）和美国病理学家学院（CAP）代表组成的工作组，重新审视和修订序列变异解释的标准和指南。该小组由临床实验室主任和临床医生组成。本报告代表了工作组的专家意见以及 ACMG、AMP 和 CAP 利益相关者的意见。这些建议主要适用于临床实验室使用的广泛基因测试，包括基因分型、单基因、组合、外显子组和基因组。本报告建议使用特定的标准术语：“致病性”、“可能致病性”、“意义不确定”、“可能良性”和“良性”来描述孟德尔疾病中发现的变异。此外，该建议描述了基于使用典型类型的变异证据（例如群体数据、计算数据、功能数据、隔离数据等）的标准将变异分类为这五个类别的过程。由于本报告中描述的临床基因检测的分析和解释变得更加复杂，ACMG 强烈建议临床分子遗传学检测应在 CLIA 批准的实验室中进行，并由委员会认证的临床分子遗传学家或分子遗传病理学家或同等人员对结果进行解释。
The American College of Medical Genetics and Genomics (ACMG) previously developed guidance for the interpretation of sequence variants. In the past decade, sequencing technology has evolved rapidly with the advent of high-throughput next generation sequencing. By adopting and leveraging next generation sequencing, clinical laboratories are now performing an ever increasing catalogue of genetic testing spanning genotyping, single genes, gene panels, exomes, genomes, transcriptomes and epigenetic assays for genetic disorders. By virtue of increased complexity, this paradigm shift in genetic testing has been accompanied by new challenges in sequence interpretation. In this context, the ACMG convened a workgroup in 2013 comprised of representatives from the ACMG, the Association for Molecular Pathology (AMP) and the College of American Pathologists (CAP) to revisit and revise the standards and guidelines for the interpretation of sequence variants. The group consisted of clinical laboratory directors and clinicians. This report represents expert opinion of the workgroup with input from ACMG, AMP and CAP stakeholders. These recommendations primarily apply to the breadth of genetic tests used in clinical laboratories including genotyping, single genes, panels, exomes and genomes. This report recommends the use of specific standard terminology: ‘pathogenic’, ‘likely pathogenic’, ‘uncertain significance’, ‘likely benign’, and ‘benign’ to describe variants identified in Mendelian disorders. Moreover, this recommendation describes a process for classification of variants into these five categories based on criteria using typical types of variant evidence (e.g. population data, computational data, functional data, segregation data, etc.). Because of the increased complexity of analysis and interpretation of clinical genetic testing described in this report, the ACMG strongly recommends that clinical molecular genetic testing should be performed in a CLIA-approved laboratory with results interpreted by a board-certified clinical molecular geneticist or molecular genetic pathologist or equivalent.