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 master DNA damage-response kinase whose biallelic loss of function causes ataxia telangiectasia and whose monoallelic loss-of-function alleles increase breast, pancreatic and prostate cancer risk, so a rare ATM missense change such as p.Asn2106Ile is assessed for both the recessive ataxia-telangiectasia mechanism and the dominant cancer-predisposition mechanism, with the variant's rarity in gnomAD currently its only supporting evidence.