Characterization of the alternatively-spliced ATM exon 7

This dataset contains fragment analysis and sequencing files of a comprehensive study of the alternatively-spliced exon 7 of the breast cancer susceptibility gene ATM. Regulation of alternative splicing is a multifactorial process that includes a wide array of regulatory sequences (SRE) such as splicing enhancers and silencers. We have bioinformatically and functionally mapped two SRE-rich regions within ATM exon 7. Then, we tested 2 control splice-site and 48 regulatory variants in minigene mgATM_4-9 with exons 4 to 9 that we had previously reported (Bueno-Martinez et al, 2022; PMID 35716007). A large fraction of SRE-variants (71%; 34/48) impaired exon 7 recognition, supporting suitability of the combined in silico and minigene approach. Nineteen variants showed strong impacts, producing higher expression levels of △(E7)-transcripts and <30% of the minigene full-length transcript. Finally, eight variants were classified as likely pathogenic according to the ACMG/AMP-based guidelines for the ATM gene.