ClinVar 中的再分类数据：“可能致病”真的有 90%的可能性吗？
Is 'likely pathogenic' really 90% likely? Reclassification data in ClinVar.
机构信息
Medical & Population Genetics Program and Genomics Platform, Broad Institute of MIT and Harvard, Main Street, Cambridge, MA, 02142, USA.
Department of Pathology, Harvard Medical School, Shattuck Street, Boston, MA, 02115, USA.
出版信息
Genome Med. 2019 Nov 21;11(1):72. doi: 10.1186/s13073-019-0688-9.
Abstract
In 2015, professional guidelines defined the term 'likely pathogenic' to mean with a 90% chance of pathogenicity. To determine whether current practice reflects this definition, ClinVar classifications were tracked from 2016 to 2019. During that period, between 83.8 and 99.1% of likely pathogenic classifications were reclassified as pathogenic, depending on whether LP to VUS reclassifications are included and on how these classifications are categorized.
摘要
2015 年，专业指南将“很可能致病”定义为致病性概率为 90%。为了确定当前的实践是否反映了这一定义，我们从 2016 年到 2019 年跟踪了 ClinVar 分类。在此期间，根据是否包括 LP 到 VUS 的重新分类，以及如何对这些分类进行分类，很可能致病的分类中有 83.8%至 99.1%被重新分类为致病性。
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本文引用的文献
1
Variant classification changes over time in BRCA1 and BRCA2.BRCA1 和 BRCA2 中的变异分类随时间变化。
Genet Med. 2019 Oct;21(10):2248-2254. doi: 10.1038/s41436-019-0493-2. Epub 2019 Apr 11.
2
A survey assessing adoption of the ACMG-AMP guidelines for interpreting sequence variants and identification of areas for continued improvement.一项评估采用美国医学遗传学与基因组学学会-美国病理学家协会（ACMG-AMP）解读序列变异指南及确定持续改进领域情况的调查。
Genet Med. 2019 Aug;21(8):1699-1701. doi: 10.1038/s41436-018-0432-7. Epub 2019 Jan 23.
3
Prevalence of Variant Reclassification Following Hereditary Cancer Genetic Testing.遗传性癌症基因检测后变异再分类的流行率。
JAMA. 2018 Sep 25;320(12):1266-1274. doi: 10.1001/jama.2018.13152.
4
The impact of variant classification on the clinical management of hereditary cancer syndromes.变异分类对遗传性癌症综合征临床管理的影响。
Genet Med. 2019 Feb;21(2):426-430. doi: 10.1038/s41436-018-0063-z. Epub 2018 Jun 6.
5
ClinVar: improving access to variant interpretations and supporting evidence.ClinVar：改善变异解读和支持证据的获取。
Nucleic Acids Res. 2018 Jan 4;46(D1):D1062-D1067. doi: 10.1093/nar/gkx1153.
6
Recommendations for reporting of secondary findings in clinical exome and genome sequencing, 2016 update (ACMG SF v2.0): a policy statement of the American College of Medical Genetics and Genomics.临床外显子组和基因组测序中次要发现报告的建议，2016年更新版（美国医学遗传学与基因组学学会次要发现v2.0）：美国医学遗传学与基因组学学会政策声明
Genet Med. 2017 Feb;19(2):249-255. doi: 10.1038/gim.2016.190. Epub 2016 Nov 17.
7
Analysis of protein-coding genetic variation in 60,706 humans.对60706名人类的蛋白质编码基因变异进行分析。
Nature. 2016 Aug 18;536(7616):285-91. doi: 10.1038/nature19057.
8
Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.序列变异解读的标准与指南：美国医学遗传学与基因组学学会和分子病理学协会的联合共识推荐
Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.
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