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更新了来自ClinGen RASopathy专家小组的变异解释和基因修复的ACMG/AMP规范

Emma H Wilcox^1,2, Ryan F Webb¹, Kezang C Tshering¹

¹Medical and Population Genetics Program, Broad Institute of MIT and Harvard, Cambridge, MA.

Genetics in medicine open

|June 11, 2025

概括

更新的RASopathy变体分类指南提高了对衰退性疾病和外基因组/基因组病例的准确性. 这些精细的规范改善了对罕见的门德尔疾病的遗传变异解释.

科学领域:

遗传学是一个遗传学.
基因组医学是基因组医学.
分子生物学分子生物学

背景情况:

临床基因RAS (RAS) 变异治疗专家小组 (VCEP) 开发了美国医学遗传学与基因组学学院 (ACMG) 和分子病理学协会 (AMP) 变异分类框架的初步规范.
对RASopathies的不断发展的理解和新的遗传测试算法需要对这些规范进行更新,以提高准确性.

研究的目的:

根据RASopathy知识和遗传测试的进步,为ACMG/AMP框架更新RASopathy变异分类规范.
为了提高RASopathies变异分类的一致性和准确性.

主要方法:

拉斯基因治疗专家小组重新评估了六种基因疾病关系和以前的规范.
为ACMG/AMP框架制定了更新的RASopathy规范.
通过重新评估59个先前分类的变体和88个新的试点变体,验证了更新规范的性能.

主要成果:

五种基因与疾病的关系被升级为"确定的"分类,一个为"中度"分类.
更新的规范适用于11个支配性和3个衰退性遗传标准,以及与ClinGen序列变异解释工作组一致的4个标准.
与之前的RAS VCEP或ClinVar分类相比,变异重新评估显示没有显著差异.

结论:

更新后的RASopathy规范显著改善了通过外基因组/基因组测序分析的衰退性疾病和病例的变异分类.
这些精细的规范可以作为一个基本框架来分类其他罕见的门德尔乱的变体.

关键词:

在ClinGen中,使用ClinGen.在中午,中午.拉索病症是一种RAS病症.拉斯/马普克 (Ras/MAPK) 是一种变体解释的变体解释

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相关概念视频

The Ras Gene

The Ras Gene

The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a...