Germline variants of BAP1 in the Australian population.

e13534Background: Germline mutations in the BRCA1-associated protein (BAP1) gene are linked to a large spectrum of cancers, defined as the BAP1 tumour predisposition syndrome (BAP1-TPDS). The cancers usually occurring in kindreds with BAP1-TPDS are uveal melanoma, mesothelioma, cutaneous melanoma, renal cell carcinoma, cholangiocarcinoma and meningioma. A 2017 review identified only 87 probands worldwide with germline BAP1 mutations. Methods: To better understand the frequency of BAP1-TPDS, we took a systematic BAP1 sequencing approach of a defined population. We screened Queensland uveal melanoma probands and their families for mutations in BAP1 (n = 64), identified variants from published studies from Australia and liaised with clinical genetics services Australia-wide to ascertain BAP1 germline variants. Only variants with a population frequency of < 0.0005 were considered. Results: We identified 2 truncating, 1 missense, 2 synonymous, 1 intronic and 1 promoter variant in the sequencing screen (7/64). ...