InterVar: Clinical Interpretation of Genetic Variants by the 2015 ACMG-AMP Guidelines

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• 作者：Quan Li¹ ; ⁴ ; Kai Wang¹ ; ² ; ³ ; ^{kw2701@cumc.columbia.edu}
• 关键词：InterVar ; variant annotation ; variant interpretation ; clinical interpretation ; ClinVar ; genetic diagnosis ; ACMG ; ANNOVAR
• 刊名：The American Journal of Human Genetics
• 出版年：2017
• 出版时间：2 February 2017
• 年：2017
• 卷：100
• 期：2
• 页码：267-280
• 全文大小：1440 K
• 卷排序：100

文摘

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.