ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.3102T>G (p.Tyr1034Ter)

dbSNP: rs780240314
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Hereditary Breast, Ovarian and Pancreatic Cancer Variant Curation Expert Panel, ClinGen RCV003985408 SCV004565383 pathogenic Familial cancer of breast 2024-01-25 reviewed by expert panel curation The c.3102T>G (p.Tyr1034Ter) variant in ATM is a nonsense variant predicted to cause a premature stop codon in a biologically-relevant-exon leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism. This alteration results in a termination codon upstream of the most C-terminal pathogenic alteration (ATM p.Arg3047*), as classified by the HBOP VCEP, and is expected to be more deleterious. This variant is absent from gnomAD v.2.1.1. This variant has been detected in at least 4 individuals with Ataxia-Telangiectasia (PMID: 26896183, 18321536, 33547824). In summary, this variant meets criteria to be classified as pathogenic for autosomal dominant hereditary breast cancer and autosomal recessive Ataxia-Telangiectasia based on the ACMG/AMP criteria applied, as specified by the HBOP VCEP. (PVS1, PM3_strong, PM2_Supporting , PM5_Supporting)
Counsyl RCV000672308 SCV000797405 likely pathogenic Ataxia-telangiectasia syndrome 2018-01-24 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000672308 SCV002211349 pathogenic Ataxia-telangiectasia syndrome 2022-04-27 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Tyr1034*) in the ATM gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ATM are known to be pathogenic (PMID: 23807571, 25614872). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with clinical features of ataxia-telangiectasia (PMID: 10980530, 18321536, 33547824). ClinVar contains an entry for this variant (Variation ID: 556315). For these reasons, this variant has been classified as Pathogenic.
Myriad Genetics, Inc. RCV003985408 SCV004931385 pathogenic Familial cancer of breast 2024-01-18 criteria provided, single submitter clinical testing This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation.

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