基因特异性ACMG/AMP分类标准用于生殖线APC变异:ClinGen InSiGHT遗传性结肠癌/多重症变异治愈专家小组的建议
Isabel Spier1, Xiaoyu Yin2, Marcy Richardson3
1Institute of Human Genetics, Medical Faculty, University of Bonn, Bonn, Germany; National Center for Hereditary Tumor Syndromes, University Hospital Bonn, Bonn, Germany; European Reference Network on Genetic Tumour Risk Syndromes (ERN GENTURIS) - Project ID No 739547.
概括
遗传性结直肠癌/多症变异愈专家小组 (VCEP) 制定了新的指导方针,用于解释与家族腺多症相关的APC基因变异. 这些标准减少了不确定的分类,提高了遗传性结直肠癌的诊断准确度.
科学领域:
- 遗传学和基因组学 在
- 在瘤学瘤学.
- 生物信息学是一种生物信息学.
背景情况:
- 家族性腺多重症 (FAP) 是一种常见的遗传多重症综合征.
- 精确解释生殖线APC变异对于诊断FAP至关重要.
- 现有的变种分类准则要求对APC进行基因特异性改进.
研究的目的:
- 开发和验证基因特异性推,用于解释生殖系APC变异.
- 改进美国医学遗传学与基因组学学院/分子病理学协会 (ACMG/AMP) 对APC的变异分类准则.
- 改善与遗传性结直肠癌相关的变体的分类.
主要方法:
- 建立了APC变种策划专家小组 (VCEP).
- 严格的数据库分析,文献审查和专家提取.
- 使用试点变种分类推导和验证APC特定标准.
主要成果:
- 开发了APC变种解释的基因和疾病信息标准.
- 实施了对等位基频率的定量方法和切断变异的逐步工具.
- 47%的试点变种被重新分类,其中不确定的意义 (VUS) 的变种减少了56%.
结论:
- 新的APC特定的ACMG/AMP标准有效地减少了VUS,并提高了变种分类的准确性.
- 这些标准保持了良好的特征变异的分类,同时提高了诊断清晰度.
- 该APC VCEP将继续为遗传性结直肠癌的临床使用提供权威的变异分类.
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