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Germline BRCA1/2 Variants in Polish Patients with Family History of Breast and Ovarian Cancer: Prevalence, CNV Detection, and Identification of a Novel Loss-of-Function Mutation

Background/Objectives: Pathogenic and likely pathogenic variants in the BRCA1 and BRCA2 genes are associated with a significantly increased risk of breast and/or ovarian cancer. We investigated genetic variants in a cohort of 450 unaffected individuals with a family history of breast and/or ovarian cancer, involving at least one first-degree relative. Methods: Next-generation sequencing (NGS) was used to analyze the coding regions of these two genes, with copy number variation (CNV) analysis. Results: A total of 16 unique to our cohort variants classified as pathogenic or likely pathogenic were identified in 22 patients, including one novel loss-of-function variant in BRCA1 gene. Furthermore, we identified a deletion of exon 21 in the BRCA1 gene in two patients. Conclusions: These results emphasize the difficulties involved in molecular diagnostics and indicate the need for further research into new predictive models for patients with hereditary breast and ovarian cancer.