Genomic sequencing advances have increased the potential to identify secondary findings (SFs). Current guidelines recommend the analysis of 59 medically actionable genes; however, patient preferences indicate interest in learning a broader group of SFs. We aimed to develop an analytical pipeline for the efficient analysis and return of all clinically significant SFs. We developed a pipeline consisting of comprehensive gene lists for five categories of SFs and filtration parameters for prioritization of variants in each category. We applied the pipeline to 42 exomes to assess feasibility and efficiency. Comprehensive lists of clinically significant SF genes were curated for each category: (1) 90 medically actionable genes and 28 pharmacogenomic variants; (2) 17 common disease risk variants; (3) 3166 Mendelian disease genes, (4) 7 early onset neurodegenerative disorder genes; (5) 688 carrier status results. Analysis of 42 exomes using our pipeline resulted in a significant decrease (> 98%) in variants compared to the raw analysis (13,036.56 ± 59.72 raw variants/exome vs 161.32 ± 7.68 filtered variants/exome), and aided in time and costs savings for the overall analysis process. Our pipeline represents a critical step in overcoming the analytic challenge associated with returning all clinically relevant SFs to allow for its routine implementation in clinical practice.

基因组测序的进步增加了鉴定次要发现（SF）的潜力。目前的指南建议分析59种具有医学作用的基因。但是，患者的喜好表明有兴趣学习更广泛的SF。我们旨在开发一种分析管道，以有效分析和返回所有具有临床意义的SF。我们开发了一个管道，该管道由五类SF的全面基因列表和过滤参数组成，以区分每个类别中的变体。我们将管道应用于42个外显子组以评估可行性和效率。为每个类别策划了具有临床意义的SF基因的全面列表：（1）90个可药用的基因和28个药物基因组变体；（2）17种常见疾病风险变异；（3）3166个孟德尔病基因，（4）7个早发性神经退行性疾病基因；（5）688个载波状态结果。与原始分析相比，使用我们的管道对42个外显子组进行分析导致变体显着减少（> 98％）（13,036.56±59.72个原始变体/外显子组与161.32±7.68个过滤后的变体/外显子组），并节省了时间和成本整个分析过程。我们的产品线是克服与返回所有临床相关SF相关联的分析挑战的关键步骤，以使其能够在临床实践中例行实施。并帮助节省了整个分析过程的时间和成本。我们的产品线是克服与返回所有临床相关SF相关联的分析挑战的关键步骤，以使其能够在临床实践中例行实施。并帮助节省了整个分析过程的时间和成本。我们的产品线是克服与返回所有临床相关SF相关的分析挑战的关键步骤，以使其能够在临床实践中例行实施。