ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.8545C>T (rs587778080)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000478987 SCV000344844 pathogenic not provided 2016-08-15 criteria provided, single submitter clinical testing
GeneDx RCV000478987 SCV000564671 pathogenic not provided 2018-08-21 criteria provided, single submitter clinical testing This pathogenic variant is denoted ATM c.8545C>T at the cDNA level and p.Arg2849Ter (R2849X) at the protein level. The substitution creates a nonsense variant, which changes an Arginine to a premature stop codon (CGA>TGA), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant has been reported in multiple individuals with Ataxia-Telangiectasia (A-T) (Castellvi-Bel 1999, Mitui 2005, Magliozzi 2006, Chessa 2009). We consider this variant to be pathogenic.
Invitae RCV000407552 SCV000622826 pathogenic Ataxia-telangiectasia syndrome 2020-09-17 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg2849*) 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 reported in individuals affected with ataxia-telangiectasia (PMID: 10425038, 16266405, 17124347, 19691550), and an individual affected with gastrointestinal tumor (PMID: 27083775). ClinVar contains an entry for this variant (Variation ID: 133637). Loss-of-function variants in ATM are known to be pathogenic (PMID: 25614872, 23807571). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV000566641 SCV000665502 pathogenic Hereditary cancer-predisposing syndrome 2019-03-13 criteria provided, single submitter clinical testing The p.R2849* pathogenic mutation (also known as c.8545C>T), located in coding exon 57 of the ATM gene, results from a C to T substitution at nucleotide position 8545. This changes the amino acid from an arginine to a stop codon within coding exon 57. This mutation has been identified in multiple individuals of Polish or Italian ancestry with clinical diagnoses of ataxia-telangiectasia (Castellví-Bel S et al. Hum. Mutat. 1999;14(2):156-62; Mitui M et al. Ann. Hum. Genet. 2005 Nov;69(Pt 6):657-64; Chessa L et al. Ann. Hum. Genet. 2009 Sep;73(Pt 5):532-9). In addition, this mutation was also detected in an individual with an unspecified gastrointestinal cancer on a hereditary cancer panel (Seifert BA et al. Clin. Cancer Res., 2016 Aug;22:4087-4094). 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.
Color Health, Inc RCV000566641 SCV000682494 pathogenic Hereditary cancer-predisposing syndrome 2020-01-15 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000407552 SCV000694379 pathogenic Ataxia-telangiectasia syndrome 2017-08-21 criteria provided, single submitter clinical testing Variant summary: The ATM c.8545C>T (p.Arg2849X) variant results in a premature termination codon, predicted to cause a truncated or absent ATM protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (e.g. c.8977C>T, p.Arg2993X). One in silico tool predicts a damaging outcome for this variant. This variant is absent in 121276 control chromosomes and has been reported in multiple AT patients in the literature. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.
Human Genome Sequencing Center Clinical Lab, Baylor College of Medicine RCV001258124 SCV001434997 pathogenic Ataxia-telangiectasia syndrome; Breast cancer, susceptibility to 2019-06-17 criteria provided, single submitter clinical testing The c.8545C>T (p.Arg2849*) variant in the ATM gene creates a stop codon which is predicted to lead to nonsense-mediated mRNA decay. The variant has been reported in multiple patients with ataxia-telangiectasia (PMID 10425038,16266405, 17124347, 19691550) and in one individual with GI tract cancer (PMID 27083775). This variant is extremely rare in general population. Therefore, this c.8545C>T (p.Arg2849*) variant in the ATM gene is classified as pathogenic.
Practice for Gait Abnormalities, David Pomarino,Competency Network Toe Walking c/o Practice Pomarino RCV001352893 SCV001547496 likely pathogenic Toe walking 2021-01-26 criteria provided, single submitter clinical testing We conducted a clinical examination of patients about toe walking. The ATM c.8545C>T was detected in one patient. We also examined a control group of children without toe walking (100 children). In this group this variant could not be identified.
ITMI RCV000120162 SCV000084304 not provided not specified 2013-09-19 no assertion provided reference population

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