Ten Years of Incidental, Secondary, and Actionable Findings

This editorial reflects on a decade of genomic screening through the lens of ACMG Secondary Findings (SF), originally “Incidental Findings,” tracking updates from 2013 to version 3.0 in 2021, which recommends reporting pathogenic or likely pathogenic variants in 83 genes. To be included, genes must meet criteria for medical actionability and potential undiagnosed morbidity without genetic insight. The authors spotlight the recent Icelandic study by Jensson et al. (N=57,933), showing 4% of individuals carry actionable variants, with cancer-related genes (e.g. BRCA2, BRCA1) associated with the most pronounced reduction in life span (~3 years). They discuss cause-of-death concordance and variant-specific risks (LDLR, MYBPC3), highlight limitations (population homogeneity, lack of statistical adjustment), and debate the appropriateness of population screening. Despite ACMG’s stance against non-research screening, the editorial suggests the Icelandic data, alongside studies in the All of Us cohort and cost-effectiveness models, may reignite calls for tier 1 genomic screening with public health justification.

This editorial reflects on a decade of genomic screening through the lens of ACMG Secondary Findings (SF), originally “Incidental Findings,” tracking updates from 2013 to version 3.0 in 2021, which recommends reporting pathogenic or likely pathogenic variants in 83 genes. To be included, genes must meet criteria for medical actionability and potential undiagnosed morbidity without genetic insight. The authors spotlight the recent Icelandic study by Jensson et al. (N=57,933), showing 4% of individuals carry actionable variants, with cancer-related genes (e.g. BRCA2, BRCA1) associated with the most pronounced reduction in life span (~3 years). They discuss cause-of-death concordance and variant-specific risks (LDLR, MYBPC3), highlight limitations (population homogeneity, lack of statistical adjustment), and debate the appropriateness of population screening. Despite ACMG’s stance against non-research screening, the editorial suggests the Icelandic data, alongside studies in the All of Us cohort and cost-effectiveness models, may reignite calls for tier 1 genomic screening with public health justification.