P074 Mainstreaming genetic testing in dermatology: an audit of diagnostic yield and frequency of variants of uncertain significance

Abstract

Dermatologists request genetic testing as part of mainstreaming of genomics in nongenetic specialties. Data on the yield of genetics testing and the frequency of variants of uncertain significance (VUSs) returned in this context may inform service delivery. Our aim was to report the outcomes of an audit of genetic tests requested by dermatologists over a 12-month period at a tertiary centre. Genetic tests requested from 1 May 2024 to 30 April 2025 were retrieved from our genomics medicine service centre, and a retrospective case note review was performed. Six dermatologists requested 77 genetic tests during the audit period. The three most frequent requests were ‘mosaic skin disorders’ (14%), ‘ichthyosis and erythrokeratoderma’ (10%) and ‘familial melanoma’ (10%). When mapped to groupings in the National Genomic Test Directory, the majority of tests were from dermatology (56%), followed by inherited cancer (27%) panels. In total, 52 tests had an available result at the time of audit: 11 (21%) identified a pathogenic or likely pathogenic variant (PV), four reported a VUS (8%) and 37 (71%) did not identify a PV. The PV yield rate of available results was 43% for mosaic skin disorders, 60% for ichthyosis and keratoderma and 0% for familial melanoma. VUSs were identified in the following genes PLEC, LEMD3, MAP3K3 and ATP2C1. Investigations following VUS reporting involved family segregation studies and parental testing, in collaboration with the clinical genetics service. These data suggest that the majority of genetic tests in this audit were either normal or identified a PV, which can be communicated by informed dermatologists, with only a small proportion reported as a VUS. Partnership with clinical genetics, who locally have family- and person-level health records, aids investigation of VUSs. Test panel yield is variable and a larger national audit may shape testing criteria in future updates of the National Genomic Test Directory.