Management of Secondary Genomic Findings

Am J Hum Genet. 2020 Jul 2;107(1):3-14. doi: 10.1016/j.ajhg.2020.05.002.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Genetic Diseases, Inborn / diagnosis
  • Genetic Diseases, Inborn / genetics*
  • Genetic Diseases, Inborn / prevention & control
  • Genomics / methods
  • Humans
  • Medical History Taking