The wide use of gene panels has proven to be extremely useful in clinical practice due to the optimization of both time and cost, and to the identification and monitoring of high-risk families for hereditary breast cancer, harboring pathogenic germline variants in genes other than BRCA1 and BRCA2. However, the use of gene panels introduces a new dilemma: a high frequency of variants of uncertain significance (VUS). This evidence concerns the gene BRCA2 and breast cancer.