Whole-Genome Sequencing Dataset from Two High-Risk Breast Cancer Families Negative for BRCA1/2 and Other Known Susceptibility Genes

Hereditary breast cancer (BC) remains unexplained in a substantial proportion of families who test negative for BRCA1/2 and other known susceptibility genes. To contribute to the genomic characterization of these unresolved cases, we generated a whole-genome sequencing (WGS) dataset from six women belonging to two unrelated high-risk families, each comprising three sisters diagnosed with BC. All participants had previously received negative results in conventional multigene panel testing. WGS was performed on peripheral blood DNA using the Illumina NovaSeq platform, followed by variant calling against GRCh38 and the comprehensive annotation of single-nucleotide variants, indels, and structural variants. For each family, we identified shared ClinVar-annotated variants, rare exonic or splice-site alterations, and intronic variants located within a curated set of 286 cancer-related genes. The dataset includes per-patient VCF files, copy number variation annotations, and family-level variant summaries. Raw and processed data are publicly available through the Sequence Read Archive and Zenodo. This resource supports variant reinterpretation, exploration of regulatory and intronic regions, and methodological benchmarking in the study of familial BC beyond established susceptibility genes.