Recommendations for Reporting of Incidental Findings in Clinical Exome and Genome Sequencing

As exome and genome sequencing become more commonly used in medical care, doctors will increasingly be able to learn about genetic changes that increase an individual's risk for developing an unrelated disease. In the past, these incidental genetic findings (unrelated to the condition for which the patient was tested) were seldom provided to the patient.

The American College of Medical Genetics and Genomics (ACMG) has created a set of recommendations addressing incidental findings and a minimum list of conditions, genes, and variants that are recommended to be returned whenever clinical sequencing is performed. The ACMG now recommends that for the conditions on the list, the laboratory should return the incidental findings to the doctor ordering the sequencing, and those doctors should manage this information with the patient in the context of that patient's clinical presentation and family history.

Incidental, or secondary, findings, are health-related interpretations of a patient's genetic code that are unrelated to the primary reason for ordering the testing. For example, if an exome or genome sequence were ordered to help diagnose a cardiac condition, there would exist the possibility of finding a different gene that indicated a predisposition for cancer. If the cancer risk were reported to the ordering clinician as an incidental finding, the clinician and patient could explore whether to increase medical surveillance in a way that could catch a cancer earlier and reduce mortality in that patient.

The ACMG report generated a short list of well-understood conditions/genes/variants for which the possibility exists of medical intervention with high benefit to those carrying the variants if they are detected presymptomatically.