The British Society for Genetic Medicine guidance on managing incidental findings identified during rare disease genomic testing.

The use of large next-generation sequencing panels and genome-wide array analysis increases the likelihood of revealing a highly actionable variant, or a carrier status, unrelated to the reason for testing.

Genomic testing occasionally reveals a highly actionable variant unrelated to the reason for testing, relevant either to the patient or to their relatives. The British Society for Genetic Medicine has issued guidance for clinicians requesting genomic tests and for clinical scientists in NHS genomic laboratories, starting from the principle that the possibility of incidental findings should be discussed with the patient or parents before testing. The decision to report a variant unrelated to the referral reason depends on clinical actionability, penetrance and variant classification; a pathogenic variant may be reported where there is evidence of high penetrance and available treatment or surveillance likely to improve outcome. Reporting incidental heterozygous carrier status for autosomal recessive conditions is by contrast not recommended, even though large panels and genome-wide array analysis increase its frequency. The guidance provides a reporting framework with case examples and a cancer susceptibility gene list, aiming for greater consistency than case-by-case decisions, and is intended to be usable in other publicly funded health systems with developing genomic services.

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

The contribution is not conceptual — actionability, penetrance and classification are familiar criteria — but operational: a national learned society takes a written position, including the refusal to report recessive carrier status, which relieves the laboratory scientist of an individual judgement that is hard to defend to a family. The limitation is generic to the format, an expert consensus without systematic review or prospective assessment of the benefit-risk balance of reporting, and the cancer susceptibility gene list will have to keep pace with penetrance data. Transposing it outside the NHS assumes a public system in which follow-up of identified carriers is organised and funded, a condition not met everywhere.

Analysis by Dr Thibaut Benquey