Schiabor Barrett Kelly M, Masnick Max, Hatchell Kathryn E, Savatt Juliann M, Banet Natalie, Buchanan Adam, Willard Huntington F
Geisinger Research, Geisinger Health, Danville, PA, USA.
Helix OpCo, San Mateo, CA, USA.
HGG Adv. 2022 Jan 8;3(2):100086. doi: 10.1016/j.xhgg.2022.100086. eCollection 2022 Apr 14.
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 -related cancer diagnoses from electronic health records to demonstrate an association between published laboratory-based functional designations of variants and -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.
基因组变异的功能评估为系统地检查变异的潜在致病性提供了一种很有前景的方法，且无需相关临床数据。然而，要得出这样的结论需要通过适当的临床发现进行验证。为此，我们利用外显子组数据中的变异调用以及电子健康记录中的相关癌症诊断，在一个未经过筛选的患者参与者队列中，证明已发表的基于实验室的变异功能分类与相关癌症诊断之间的关联。这些发现验证并支持进一步探索功能检测数据，以更好地理解罕见变异的致病性。在健康人群基因组筛查的背景下，这些信息可能很有价值，因为许多罕见的、潜在致病性的变异可能没有足够的相关临床数据来直接指导对它们的解读。
