Combined genetic and splicing analysis of BRCA1 c.[594-2A>C; 641A>G] highlights the relevance of naturally occurring in-frame transcripts for developing disease gene variant classification algorithms
Combined genetic and splicing analysis of BRCA1 c.[594-2A>C; 641A>G] highlights the relevance of naturally occurring in-frame transcripts for developing disease gene variant classification algorithms
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DOI：
10.1093/hmg/ddw094
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发表时间：
2016-06-01
影响因子：
3.5
通讯作者：
Spurdle, Amanda B.
中科院分区：
文献类型：
--
作者：
de la Hoya, Miguel;Soukarieh, Omar;Spurdle, Amanda B.
我们确认BRCA1c.[594-2A>；C；641a>；G]不应被视为高危致病变异。重要的是，我们详细的mRNA分析结果表明，对于携带BRCA1外显子9或10的截断变异或任何其他允许20-30%肿瘤抑制功能的BRCA1等位基因的个体来说，BRCA相关癌症的风险可能不会显著增加。更广泛地说，我们的发现强调了评估自然发生的选择性剪接对于临床评估致病基因变异的重要性。
We confirm that BRCA1c.[594-2A > C;641A > G] should not be considered a high-risk pathogenic variant. Importantly, results from our detailed mRNA analysis suggest that BRCA-associated cancer risk is likely not markedly increased for individuals who carry a truncating variant in BRCA1 exons 9 or 10, or any other BRCA1 allele that permits 20-30% of tumor suppressor function. More generally, our findings highlight the importance of assessing naturally occurring alternative splicing for clinical evaluation of variants in disease-causing genes.