Secondary genomic findings are increasingly being returned to individuals as opportunistic screening results. A secondary finding offers the chance to identify and mitigate disease that may otherwise be unrecognized in an individual. As a form of screening, secondary findings must be considered differently from sequencing results in a diagnostic setting. For these reasons, clinicians should employ an evaluation and long-term management strategy that accounts for both the increased disease risk associated with a secondary finding and the lower positive predictive value of a screening result compared to an indication-based testing result. Here we describe an approach to the clinical evaluation and management of an individual who presents with a secondary finding. This approach enumerates five domains of evaluation—(1) medical history, (2) physical exam, (3) family history, (4) diagnostic phenotypic testing, and (5) variant correlation—through which a clinician can distinguish a molecular finding from a clinicomolecular diagnosis of genomic disease. With this framework, both geneticists and non-geneticist clinicians can optimize their ability to detect and mitigate genomic disease while avoiding the pitfalls of overdiagnosis. Our goal with this approach is to help clinicians translate secondary findings into meaningful recognition, treatment, and prevention of disease.

二次基因组发现越来越多地作为机会筛选结果返回给个人。次要发现提供了识别和减轻原本无法识别的疾病的机会。作为筛选的一种形式，必须将次要发现与诊断环境中的测序结果区别对待。由于这些原因，临床医生应采用评估和长期管理策略，该策略应考虑与基于次要发现的结果相比，与继发发现相关的疾病风险增加以及筛查结果的较低阳性预测值。在这里，我们描述了对具有次要发现的个体进行临床评估和管理的方法。这种方法列举了五个评估领域：（1）病史，（2）体格检查，（3）家族史，（4）诊断表型测试和（5）变异相关性-临床医生可通过此相关性将分子发现与基因组疾病的临床分子诊断区分开。有了这个框架，遗传学家和非遗传学家都可以优化其检测和缓解基因组疾病的能力，同时避免过度诊断的陷阱。我们采用这种方法的目标是帮助临床医生将次要发现转化为有意义的识别，治疗和预防疾病。遗传学家和非遗传学家都可以优化其检测和缓解基因组疾病的能力，同时避免过度诊断的陷阱。我们采用这种方法的目标是帮助临床医生将次要发现转化为有意义的识别，治疗和预防疾病。遗传学家和非遗传学家都可以优化其检测和缓解基因组疾病的能力，同时避免过度诊断的陷阱。我们采用这种方法的目标是帮助临床医生将次要发现转化为有意义的识别，治疗和预防疾病。