Frequency of genomic incidental findings among 21,915 eMERGE network participants

PURPOSE: Discovering an Incidental or Secondary Finding (IF) is a potential result of genomic testing, but little data exists describing types and frequencies of IFs likely to appear in broader clinical populations. METHODS: The Electronic Medical Records and Genomics network phase III (eMERGEIII) developed a CLIA-compliant sequencing panel of 109 genes and 1551 variants of clinical relevance or research interest and deployed this panel at 10 clinical sites. We evaluated medically actionable IFs across 67 genes and 14 SNVs in a diverse cohort of 21,915 participants drawn from a variety of settings (e.g. primary care, biobanks, specialty clinics). RESULTS: Correcting for testing indication, we found a 3.02% overall frequency of IFs; 2.54% from 59 genes the American College of Medical Genetics and Genomics recommends for IF return, and 0.48% in other genes, primarily HFE and PALB2. IFs associated with cancer susceptibility were most frequent (1.38%), followed by cardiovascular diseases (0.87%), and lipid disorders (0.50%). After removing HFE, the frequency of IFs and proportion of pathogenic vs. likely pathogenic IFs did not differ in those self-identifying as white vs. others. CONCLUSION: Here we present frequencies and types of medically actionable incidental findings to support informed decision-making by patients, participants, and practitioners engaged in genomic medicine.