Assessment of incidental findings in 232 whole-exome sequences from the Baylor-Hopkins Center for Mendelian Genomics.
Assessment of incidental findings in 232 whole-exome sequences from the Baylor-Hopkins Center for Mendelian Genomics.
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DOI：
10.1038/gim.2014.196
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发表时间：
2015-10
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2013年3月，ACMG公布了一份包含56个基因的清单，并建议应向患者报告通过临床测序偶然检测到的致病性和可能致病的变异。作为确定这一建议在研究环境中的实际后果的第一步，我们在贝勒-霍普金斯孟德尔基因组学中心的232个全外显子组序列中搜索了这些基因的变体。我们鉴定了罕见的、非同义的和剪接的SNV和插入缺失，并使用HGMD、Emory和ClinVar数据库评估了变异分类。我们分析了56个基因中每一个的突变负担，并确定哪些变异应该报告给患者。我们的过滤导致249个不同的变体，平均每个个体1.69个变体。其中一半是未被3个参考数据库中的任何一个分类的新型错义突变。在HGMD中列出的101个变体中，48个也在ClinVar中，3个也在Emory中;这些共享变体中有一半在数据库之间分类不一致。一些基因始终比其他基因具有更大的变异。总的来说，0.86%的个体有可报告的偶然变异。这些观察结果表明，目前的一些挑战，评估偶发变异咨询患者的表型后果。
In March 2013, the ACMG published a list of 56 genes with the recommendation that pathogenic and likely pathogenic variants detected incidentally by clinical sequencing should be reported to patients. As an initial step in determining the practical consequences of this recommendation in the research setting, we searched for variants in these genes in 232 whole exome sequences from the Baylor-Hopkins Center for Mendelian Genomics. We identified rare, nonsynonymous and splicing SNVs and indels and assessed variant classification using HGMD, Emory and ClinVar databases. We analyzed the burden of mutation in each of the 56 genes and determined which variants should be reported to patients. Our filtering resulted in 249 distinct variants, with a mean of 1.69 variants per individual. Half of these were novel missense mutations not classified by any of the 3 reference databases. Of 101 variants listed in HGMD, 48 were also in ClinVar and 3 were also in Emory; half of these shared variants were classified discordantly between databases. Some genes consistently had greater variation than others. In total, 0.86% of individuals had a reportable incidental variant. These observations demonstrate some current challenges of assessing phenotypic consequences of incidental variants for counseling patients.
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来自1,092个人基因组的遗传变异的综合图。
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64.8
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影响因子：
3.9
作者：
Bean, Lora J. H.;Tinker, Stuart W.;Hegde, Madhuri R.
通讯作者：
Hegde, Madhuri R.
DOI：
10.1038/gim.2013.73
发表时间：
2013-07
期刊：
Genetics in medicine : official journal of the American College of Medical Genetics
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使用下一代 DNA 测序数据进行变异发现和基因分型的框架。
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30.8
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影响因子：
4.5
作者：
Petrovski S;Wang Q;Heinzen EL;Allen AS;Goldstein DB
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Goldstein DB