Splicing Functional Assays of CHEK2 splice-site variants identified in the BRIDGES project

This dataset corresponds to a comprehensive study of splice-site variants of the breast cancer susceptibility gene CHEK2. Variant data have been obtained from the large-scale sequencing project BRIDGES that sequenced 34 genes in 113,000 women. A set of 128 CHEK2 variants at the intron-exon boundaries were identified, 52 of which were predicted spliceogenic. These were introduced into the three minigene constructs by site-directed mutagenesis and tested in MCF-7 cells. Forty-six variants impaired splicing, 26 of which were classified as pathogenic/likely pathogenic variants according to ACMG/AMP-based guidelines, so carrier patients and families may benefit from tailored prevention protocols and personalized therapies.