ATM encodes a kinase that acts as a master controller of the cellular DNA damage response: it detects double-strand breaks and coordinates DNA repair, cell cycle arrest, or apoptosis through downstream targets including p53, BRCA1, and CHK2. Loss-of-function mutations in both copies of ATM cause ataxia telangiectasia, an autosomal recessive disorder characterized by neurological problems, immune deficiency, and cancer predisposition. ATM functions as a tumor suppressor: individuals with ataxia telangiectasia are prone to childhood lymphomas, leukemias, and breast cancer, while carriers of a single altered copy have increased risk of breast, pancreatic, prostate, and other cancers. Somatic ATM mutations also occur in lymphoid malignancies and solid tumors, and ATM-deficient cancers are often especially sensitive to DNA-damaging treatments.

ATM is a tumor suppressor whose loss-of-function mutations cause ataxia telangiectasia when biallelic and increase cancer risk in single-copy carriers. This Pathogenic frameshift truncates the ATM kinase and is predicted to trigger nonsense-mediated decay, so it is expected to abolish ATM function and carry clinical significance for cancer risk in this individual and family.