Sequencing-based genetic tests have uncovered a vast array of BRCA2 variants. The number of observed variants continues to increase due to expanding therapeutic options and improved sampling. With rapid advances in high-throughput molecular and bioinformatic pipelines for sequencing, the bottleneck in genetic testing has shifted to the clinical interpretation of variants. Due to limited clinical, familial and epidemiological data, thousands of variants are considered to be variants of unknown significance (VUS). As of April 11, 2025, ClinVar includes 19,927 BRCA2 variants, with 9,543 classified as VUS. These predominantly missense and intronic alterations cannot be effectively utilized in clinical care. Furthermore, interpreting variants in genes like BRCA2, which predispose individuals to breast cancer, is challenging. Breast cancer is common, which makes it difficult to distinguish between cases caused by germline mutations and sporadic cases. Assessing pathogenicity through genotype-phenotype correlations is also limited, as many VUS are rare and appear in only one person or family, making statistical modeling difficult. This uncertainty in variant interpretation can lead to both over- and undertreatment, impacting patient care and healthcare costs. Our research aims to address this by developing an in vivo zebrafish model to study BRCA2 variants. This will address the gap in clinical interpretation of VUS by providing robust functional readouts. Accurate classification will benefit clinical practice by improving patient care, reducing healthcare costs and enhancing the overall efficiency of genetic testing. These advances will positively impact patients with VUS in BRCA2, their healthcare providers, diagnostic laboratories and public health as a whole.