Splice-site variants of the breast cancer susceptibility gene ATM. BRIDGES_Project-2

This dataset contains fragment analysis and sequencing files of the impact on splicing of splice-site variants in 17 exons of the breast cancer susceptibility gene ATM. Splicing dysregulation is a well-established mechanism of pathogenicity for variants in disease susceptibility genes. Pathogenic germline variants in ATM are associated with a 20–30% lifetime risk of breast cancer. We aimed to carry out splicing analysis of ATM splice-site variants detected in subjects of the large-scale sequencing project BRIDGES (https://cordis.europa.eu/project/id/634935) by minigene assays. To this end, we bioinformatically selected 47 splice-site variants in 17 exons that were genetically engineered into three minigenes and assayed in MCF-7 cells. Aberrant splicing was observed in 38 variants. Of these, 29 showed no or negligible minigene full-length (mgFL) transcript expression, including eight exonic variants (7 missense and one nonsense). All minigene read-outs from variants were interpreted according to the ACMG/AMP (American College of Medical Genetics and Genomics/Association for Molecular Pathology)-based specifications for the ATM gene.