ClinVar

Description

A copy number variant was detected in the ATM gene. The deleted region encompases exons 37 to 43. Heterozygous partially deletions in the ATM gene are published as disease causing (PMID 27664052, 6681312). This CNV contains 208 loss-of-function causing variants, and and a coding region of a loss-of-function gene. Heterozygous pathogenic variants in the ATM gene cause familial breast cancer susceptibility (OMIM# 114480). The cancer risk of individuals heterozygous for an ATM pathogenic variant is approximately four times that of the general population, primarily because of the increased risk for breast cancer. Potentially, it may increase the risk of ovarian cancer. There is insufficient evidence to suggest increased risk for pancreatic cancer. Homozygous or compound heterozygous mutations in the ATM gene are associated with ataxia- telangiectasia (A-T). Classic ataxia-telangiectasia is characterized by progressive cerebellar ataxia beginning between ages 1 and 4 years, oculomotor apraxia, choreoathetosis, telangiectasias of the conjunctivae, immunodeficiency, frequent infections, and an increased risk for malignancy, particularly leukemia and lymphoma. Individuals with A-T are unusually sensitive to ionizing radiation. Nonclassic forms of A-T have included adult-onset A-T and A-T with early-onset dystonia.