Abstract P05: Comprehensive Analysis of BAP1 Germline Variants

Abstract

Germline mutations in the BRCA1-associated protein 1 (BAP1) gene are linked to various hereditary cancer syndromes, particularly BAP1 tumor predisposition syndrome. However, the effects of these mutations on cellular biology and their roles in disease predisposition are not well understood. This lack of knowledge hinders clinical and research efforts to develop therapies for at-risk individuals and their families. Here, we propose a comprehensive approach combining traditional functional assays with advanced technologies such as next-generation sequencing and in silico modelling to analyze and compare the impacts of different BAP1 mutations on cellular functions. We applied this method to examine various BAP1 germline variants, including benign, pathogenic, and variants of unknown significance, demonstrating its utility in BAP1 variant classification. This approach may enable clinicians to reliably differentiate between pathogenic and benign BAP1 variants and may facilitate the rapid assessment of newly identified BAP1 germline variants. Classifying new BAP1 germline variants helps inform predisposed patients and their families about potential cancer risks, allowing for timely clinical interventions when necessary.