ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.1122_1123del (p.Glu376fs) (rs1591517571)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV001009889 SCV001170014 pathogenic Hereditary cancer-predisposing syndrome 2019-08-16 criteria provided, single submitter clinical testing The c.1122_1123delAA variant, located in coding exon 8 of the ATM gene, results from a deletion of two nucleotides at nucleotide positions 1122 to 1123, causing a translational frameshift with a predicted alternate stop codon (p.E376Ifs*2). This alteration has been reported with a carrier frequency of 0.000 in 53 unselected male breast cancer patients and 0.0001 in 12490 male controls of Japanese ancestry (Momozawa Y et al. Nat Commun, 2018 10;9:4083). This alteration (designated as c.1121_1122delAA) has also been reported in the compound heterozygous state in a patient affected with ataxia telangiectasia (Nakayama T et al. Brain Dev., 2015 Mar;37:362-5). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Cancer Genomics Group,Japanese Foundation For Cancer Research RCV001030518 SCV001193466 likely pathogenic Hereditary breast and ovarian cancer syndrome 2019-05-01 criteria provided, single submitter research
Invitae RCV001385543 SCV001585432 pathogenic Ataxia-telangiectasia syndrome 2020-10-29 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Glu376Ilefs*2) in the ATM gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with ataxia telangiectasia (PMID: 24954719) and in an individual with breast cancer (PMID: 32566746). This variant is also known as c.1121_1122delAA in the literature. ClinVar contains an entry for this variant (Variation ID: 818362). Loss-of-function variants in ATM are known to be pathogenic (PMID: 23807571, 25614872). For these reasons, this variant has been classified as Pathogenic.

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