Clinical validation of genomic functional screen data: Analysis of observed BRCA1 variants in an unselected population cohort.
Clinical validation of genomic functional screen data: Analysis of observed BRCA1 variants in an unselected population cohort.
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DOI：
10.1016/j.xhgg.2022.100086
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发表时间：
2022-04-14
期刊：
影响因子：
--
通讯作者：
Willard HF
中科院分区：
文献类型：
--
作者：
Schiabor Barrett KM;Masnick M;Hatchell KE;Savatt JM;Banet N;Buchanan A;Willard HF
基因组变异的功能评估提供了一种有前途的方法，可以独立于相关临床数据系统地检查变异的潜在致病性。然而，做出这样的结论需要用适当的临床发现进行验证。为此，我们在这里使用来自外显子组数据的变异调用和来自电子健康记录的 BRCA1 相关癌症诊断来证明在未经选择的患者参与者队列中已发表的基于实验室的 BRCA1 变异功能名称与 BRCA1 相关癌症诊断之间的关联。这些发现验证并支持对功能测定数据的进一步探索，以更好地了解罕见变异的致病性。这些信息在健康人群基因组筛查的背景下可能很有价值，其中许多罕见的潜在致病变异可能没有足够的相关临床数据来直接告知其解释。基于实验室的功能测定有望预测人群中罕见变异的致病性。夏博尔·巴雷特等人。研究表明，对 BRCA1 基因变异的功能评估可区分 BRCA1 相关癌症发病率增加的个体，这反映了已发表的通过基于适应症的测试检测到的致病性 BRCA1 变异个体的癌症发病率。
Functional assessment of genomic variants provides a promising approach to systematically examine the potential pathogenicity of variants independent of associated clinical data. However, making such conclusions requires validation with appropriate clinical findings. To this end, here, we use variant calls from exome data and BRCA1-related cancer diagnoses from electronic health records to demonstrate an association between published laboratory-based functional designations of BRCA1 variants and BRCA1-related cancer diagnoses in an unselected cohort of patient-participants. These findings validate and support further exploration of functional assay data to better understand the pathogenicity of rare variants. This information may be valuable in the context of healthy population genomic screening, where many rare, potentially pathogenic variants may not have sufficient associated clinical data to inform their interpretation directly. Lab-based functional assays hold promise for predicting the pathogenicity of rare variants in populations. Schiabor Barrett et al. show that a functional assessment of BRCA1 gene variants distinguished individuals with increased rates of BRCA1-related cancers that mirrored published cancer rates in individuals with pathogenic BRCA1 variants detected by indication-based testing.
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