临床遗传变异分类的科学与艺术及其对检测准确性的影响。

IF 7.7 2区 生物学 Q1 GENETICS & HEREDITY
Hunter H Giles, Madhuri R Hegde, Elaine Lyon, Christine M Stanley, Iain D Kerr, Megan E Garlapow, Julie M Eggington
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引用次数: 1

摘要

临床遗传变异分类科学是临床遗传学和基因组学的一个新兴分支。该领域的持续改进对于生殖系(遗传)和体细胞(肿瘤学)领域精准医学的成功至关重要。本文综述了新一代DNA测序检测的变异分类。我们首先总结了目前变异发现和定义的局限性,然后分别描述了目前在生殖系和体细胞试验的主流标准和指南出版物中概述的五层和四层分类系统。然后,我们讨论了变异分类不一致性的度量和该领域对阳性结果的偏差,以及在包含估计的变异分类不完善的阳性预测值估计的背景下对小组大小和人群筛选的考虑。最后,我们分享了一些使用最广泛的标准和指南出版物的作者以及其他领域专家对变体分类现状的看法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The Science and Art of Clinical Genetic Variant Classification and Its Impact on Test Accuracy.

Clinical genetic variant classification science is a growing subspecialty of clinical genetics and genomics. The field's continued improvement is essential for the success of precision medicine in both germline (hereditary) and somatic (oncology) contexts. This review focuses on variant classification for DNA next-generation sequencing tests. We first summarize current limitations in variant discovery and definition, and then describe the current five- and four-tier classification systems outlined in dominant standards and guideline publications for germline and somatic tests, respectively. We then discuss measures of variant classification discordance and the field's bias for positive results, as well as considerations for panel size and population screening in the context of estimates of positive predictive value thatincorporate estimated variant classification imperfections. Finally, we share opinions on the current state of variant classification from some of the authors of the most widely used standards and guideline publications and from other domain experts.

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来源期刊
CiteScore
14.90
自引率
1.10%
发文量
29
期刊介绍: Since its inception in 2000, the Annual Review of Genomics and Human Genetics has been dedicated to showcasing significant developments in genomics as they pertain to human genetics and the human genome. The journal emphasizes genomic technology, genome structure and function, genetic modification, human variation and population genetics, human evolution, and various aspects of human genetic diseases, including individualized medicine.
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