M-CAP eliminates a majority of variants of uncertain significance in clinical exomes at high sensitivity
M-CAP eliminates a majority of variants of uncertain significance in clinical exomes at high sensitivity
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DOI：
10.1038/ng.3703
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发表时间：
2016-12-01
期刊：
影响因子：
30.8
通讯作者：
Bejerano, Gill
中科院分区：
文献类型：
--
作者：
Jagadeesh, Karthik A.;Wenger, Aaron M.;Bejerano, Gill
变异致病性分类器，如SIFT，PolyPhen-2，CADD和MetaLR，通过将一些变异降低为可能是良性的，有助于解释典型患者基因组中的数百种罕见的错义变异。这些广泛使用的方法错误分类了26%至38%的已知致病性突变，如果分类器在临床环境中被认为是确定的，则可能导致漏诊。我们开发了M-CAP，这是一种临床致病性分类器，在所有阈值下都优于现有方法，并以95%的灵敏度正确排除了典型基因组中60%的不确定意义的罕见错义变体。
Variant pathogenicity classifiers such as SIFT, PolyPhen-2, CADD, and MetaLR assist in interpretation of the hundreds of rare, missense variants in the typical patient genome by deprioritizing some variants as likely benign. These widely used methods misclassify 26 to 38% of known pathogenic mutations, which could lead to missed diagnoses if the classifiers are trusted as definitive in a clinical setting. We developed M-CAP, a clinical pathogenicity classifier that outperforms existing methods at all thresholds and correctly dismisses 60% of rare, missense variants of uncertain significance in a typical genome at 95% sensitivity.