Precision Health Genetic Screening: Protocol and results categories for a clinical population genetic screening program.

Population genetic screening targeting three CDC Tier 1 conditions — hereditary breast and ovarian cancer, Lynch syndrome and familial hypercholesterolaemia — with results categorised according to their alignment with personal and family history

Population genetic screening is expanding as sequencing costs fall, and the authors describe a clinical programme embedded in a large health system. The UNC Precision Health Genetic Screen analyses three CDC Tier 1 conditions: hereditary breast and ovarian cancer, Lynch syndrome and familial hypercholesterolaemia. From summer 2021 through March 2026, 348 results were returned: 331 negative and 16 positive, comprising 8 hereditary breast and ovarian cancer, 4 Lynch syndrome and 4 familial hypercholesterolaemia; one negative result was later reclassified, an unreported variant of uncertain significance becoming likely pathogenic, bringing the total to 17 positives. The team developed six internal categories placing each result in the context of reported personal and family history: among negatives, 208 were aligned with the history provided, 113 unaligned with family history and 11 unaligned with personal history. The authors stress that this categorisation helps identify participants for whom diagnostic testing would have been warranted and limits false reassurance after a negative screen.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

The 113 negatives unaligned with family history are the real finding here: a third of participants leave reassured by a screen that did not cover their actual risk. This is the blind spot of any population screening limited to a few genes, and the proposed remedy — systematic categorisation of negatives against family history — is simple and transferable to any programme. With 348 results and 17 positives, this is a programme experience report, not a performance evaluation.

Analysis by Dr Thibaut Benquey