A method of screening a subject for susceptibility to functional-ATM protein deficiency, wherein the screening comprises determining the presence of a nonthymine variant residue rs609261 located at position -3 relative to the 3 splice site of a non-sense mediated RNA decay switch exon NSE (cryptic exon in ATM intron 28) of the human genome, wherein the presence of a non-thymine variant residue rs609261 indicates that the subject has, or is susceptible to, functional-ATM protein deficiency. In some embodiments, also included herein are compositions and methods of modulating protein expression that uses an agent that targets a transposed element, methods of treatment and kits for detection of the mutation. Alternatively claimed are similar methods wherein the mutation is at rs4988000 in the ATM pseudoexon (PE), or methods of NSE gene/protein modulation.
