InterVar: Clinical Interpretation of Genetic Variants by the 2015 ACMG-AMP Guidelines
InterVar: Clinical Interpretation of Genetic Variants by the 2015 ACMG-AMP Guidelines
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DOI：
10.1016/j.ajhg.2017.01.004
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发表时间：
2017-02-02
影响因子：
9.8
通讯作者：
Wang, Kai
中科院分区：
文献类型：
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作者：
Li, Quan;Wang, Kai
2015年，美国医学遗传学和基因组学学院（ACMG）和分子病理学协会（AMP）发布了基于28项标准的人类疾病序列变异临床解释的更新标准和指南。然而，由于对这些准则的不同理解以及缺乏实现它们的标准算法等原因，个体解释者之间的差异可能很大，但用于半自动变体解释的计算工具不可用。为了解决这些问题，我们提出了一套实现这些标准的方法，并开发了一种名为InterVar的工具，以帮助人类评审员解释变异的临床意义。InterVar可以将预注释或VCF文件作为输入，并根据18个标准自动生成解释。此外，我们还开发了一个配套的网络服务器，wInterVar，使用户友好的变量解释与自动解释步骤和手动调整步骤。这些工具对于解决严重的先天性或非常早发型的高发育障碍特别有用。使用一些已发表的测序研究的结果，我们证明了InterVar在显著减少解释序列变异临床意义的时间方面的实用性。
In 2015, the American College of Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology (AMP) published updated standards and guidelines for the clinical interpretation of sequence variants with respect to human diseases on the basis of 28 criteria. However, variability between individual interpreters can be extensive because of reasons such as the different understandings of these guidelines and the lack of standard algorithms for implementing them, yet computational tools for semi-automated variant interpretation are not available. To address these problems, we propose a suite of methods for implementing these criteria and have developed a tool called InterVar to help human reviewers interpret the clinical significance of variants. InterVar can take a pre-annotated or VCF file as input and generate automated interpretation on 18 criteria. Furthermore, we have developed a companion web server, wInterVar, to enable user-friendly variant interpretation with an automated interpretation step and a manual adjustment step. These tools are especially useful for addressing severe congenital or very early-onset developmental disorders with high penetrance. Using results from a few published sequencing studies, we demonstrate the utility of InterVar in significantly reducing the time to interpret the clinical significance of sequence variants.