The Manchester score-(MS) was developed-(2004) to assess the likelihood of BRCA1/2 pathogenic variants-(PV) in breast/ovarian cancer cases with MS=15/20 being the threshold for 10/20% detection rates. We have now evaluated MS in >10,000 breast/ovarian cancers. Overall, 6744 breast and 3291 ovarian cases were tested. For breast, 453-(6.7%) PVs were detected in BRCA1 and 456-(6.8%) in BRCA2-(combined-13.5%). Combined detection with MS=13-14, 15-19 and 20-24 was 52/821-(6.3%), 168/1440-(11.7%) and 193/877-(22.0%) respectively. For ovarian, detection rates were 273-(8.3%) and 193-(5.9%) for BRCA1/BRCA2 respectively. The MS 15-19-(10%) threshold held true for all age groups and breast/ovarian pathology types, except grade-1 breast-(not associated). MS remains a robust tool to estimate BRCA1/BRCA2 likelihood. (By Professor Evans Gareth, https://jmg.bmj.com/content/early/2025/11/19/jmg-2025-110869 )

The authors