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NM_000051.4(ATM):c.7913G>A (p.Trp2638Ter)

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Interpretation:
Pathogenic/Likely pathogenic​

Review status:
criteria provided, multiple submitters, no conflicts
Submissions:
10 (Most recent: Nov 19, 2021)
Last evaluated:
Jan 4, 2021
Accession:
VCV000141233.13
Variation ID:
141233
Description:
single nucleotide variant
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NM_000051.4(ATM):c.7913G>A (p.Trp2638Ter)

Allele ID
150947
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
11q22.3
Genomic location
11: 108332886 (GRCh38) GRCh38 UCSC
11: 108203613 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
LRG_135t1:c.7913G>A
LRG_135:g.115055G>A
NC_000011.9:g.108203613G>A
... more HGVS
Protein change
W2638*
Other names
p.W2638*:TGG>TAG
Canonical SPDI
NC_000011.10:108332885:G:A
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00008
Exome Aggregation Consortium (ExAC) 0.00001
The Genome Aggregation Database (gnomAD) 0.00006
Trans-Omics for Precision Medicine (TOPMed) 0.00006
The Genome Aggregation Database (gnomAD), exomes 0.00000
Trans-Omics for Precision Medicine (TOPMed) 0.00008
The Genome Aggregation Database (gnomAD) 0.00013
Links
ClinGen: CA294097
dbSNP: rs377349459
VarSome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Pathogenic 2 criteria provided, multiple submitters, no conflicts Jan 4, 2021 RCV000129649.9
Pathogenic/Likely pathogenic 5 criteria provided, multiple submitters, no conflicts Oct 27, 2020 RCV000169621.8
Pathogenic 2 criteria provided, multiple submitters, no conflicts Dec 11, 2020 RCV000212077.5
Pathogenic 1 criteria provided, single submitter Jan 18, 2018 RCV000768151.1
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
ATM Sufficient evidence for dosage pathogenicity No evidence available GRCh38
GRCh37
6418 10309
C11orf65 - - - GRCh38
GRCh37
3 3890

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Likely pathogenic
(Feb 19, 2015)
criteria provided, single submitter
Method: literature only
Ataxia-telangiectasia syndrome
(Autosomal recessive inheritance)
Allele origin: unknown
Counsyl
Accession: SCV000221148.1
Submitted: (Mar 11, 2015)
Evidence details
Publications
PubMed (4)
Pathogenic
(Jun 01, 2018)
criteria provided, single submitter
Method: clinical testing
Hereditary cancer-predisposing syndrome
Allele origin: germline
Ambry Genetics
Accession: SCV000184447.6
Submitted: (Nov 30, 2020)
Evidence details
Publications
PubMed (6)
Comment:
The p.W2638* pathogenic mutation (also known as c.7913G>A), located in coding exon 52 of the ATM gene, results from a G to A substitution at … (more)
Pathogenic
(Oct 27, 2020)
criteria provided, single submitter
Method: clinical testing
Ataxia-telangiectasia syndrome
Allele origin: germline
Invitae
Accession: SCV000253746.7
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (9)
Comment:
This sequence change creates a premature translational stop signal (p.Trp2638*) in the ATM gene. It is expected to result in an absent or disrupted protein … (more)
Pathogenic
(Dec 11, 2020)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV000209648.14
Submitted: (Sep 25, 2021)
Evidence details
Comment:
Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Observed … (more)
Pathogenic
(May 15, 2017)
criteria provided, single submitter
Method: clinical testing
Ataxia-telangiectasia syndrome
Allele origin: germline
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000694363.1
Submitted: (Jan 25, 2018)
Evidence details
Publications
PubMed (6)
Comment:
Variant summary: The ATM c.7913G>A (p.Trp2638X) variant results in a premature termination codon, predicted to cause a truncated or absent ATM protein due to nonsense … (more)
Pathogenic
(Jul 02, 2018)
criteria provided, single submitter
Method: clinical testing
Ataxia-telangiectasia syndrome
Allele origin: unknown
Mendelics
Accession: SCV000838603.1
Submitted: (Aug 20, 2018)
Evidence details
Pathogenic
(Jan 18, 2018)
criteria provided, single submitter
Method: clinical testing
Ataxia-telangiectasia syndrome
Familial cancer of breast
Allele origin: germline
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago
Accession: SCV000898530.1
Submitted: (Dec 12, 2018)
Evidence details
Comment:
ATM NM_000051.3 exon 53 p.Trp2638* (c.7913G>A): This variant has been identified as homozygous or compound heterozygous in at least 6 individuals with ataxia telangiectasia (Sasaki … (more)
Pathogenic
(Feb 11, 2020)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: unknown
Athena Diagnostics Inc
Accession: SCV001475571.1
Submitted: (Dec 30, 2020)
Evidence details
Publications
PubMed (10)
Comment:
The variant creates a premature nonsense codon, and is therefore predicted to result in the loss of a functional protein. Found in at least one … (more)
Pathogenic
(Jan 04, 2021)
criteria provided, single submitter
Method: clinical testing
Hereditary cancer-predisposing syndrome
Allele origin: germline
Color Health, Inc
Accession: SCV000687802.3
Submitted: (Jun 11, 2021)
Evidence details
Comment:
This variant changes 1 nucleotide in exon 53 of the ATM gene, creating a premature translation stop signal. This variant is expected to result in … (more)
Pathogenic
(May 06, 2019)
no assertion criteria provided
Method: clinical testing
Ataxia-telangiectasia syndrome
Allele origin: germline
PerkinElmer Genomics
Accession: SCV002020077.1
Submitted: (Nov 19, 2021)
Evidence details

Functional evidence

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There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for this variant

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Title Author Journal Year Link
Prevalence of Inherited Mutations in Breast Cancer Predisposition Genes among Women in Uganda and Cameroon. Adedokun B Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 2020 PMID: 31871109
Assessing the effectiveness of the National Comprehensive Cancer Network genetic testing guidelines in identifying African American breast cancer patients with deleterious genetic mutations. Ademuyiwa FO Breast cancer research and treatment 2019 PMID: 31325073
Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria. Nykamp K Genetics in medicine : official journal of the American College of Medical Genetics 2017 PMID: 28492532
Male breast cancer in a multi-gene panel testing cohort: insights and unexpected results. Pritzlaff M Breast cancer research and treatment 2017 PMID: 28008555
Inherited DNA-Repair Gene Mutations in Men with Metastatic Prostate Cancer. Pritchard CC The New England journal of medicine 2016 PMID: 27433846
Pathogenic and likely pathogenic variant prevalence among the first 10,000 patients referred for next-generation cancer panel testing. Susswein LR Genetics in medicine : official journal of the American College of Medical Genetics 2016 PMID: 26681312
Ten new ATM alterations in Polish patients with ataxia-telangiectasia. Podralska MJ Molecular genetics & genomic medicine 2014 PMID: 25614872
Twelve novel Atm mutations identified in Chinese ataxia telangiectasia patients. Huang Y Neuromolecular medicine 2013 PMID: 23807571
New mutations in the ATM gene and clinical data of 25 AT patients. Demuth I Neurogenetics 2011 PMID: 21965147
Levels of gamma-H2AX Foci after low-dose-rate irradiation reveal a DNA DSB rejoining defect in cells from human ATM heterozygotes in two at families and in another apparently normal individual. Kato TA Radiation research 2006 PMID: 16953663
Five haplotypes account for fifty-five percent of ATM mutations in Brazilian patients with ataxia telangiectasia: seven new mutations. Coutinho G American journal of medical genetics. Part A 2004 PMID: 15039971
Cellular responses to ionising radiation of AT heterozygotes: differences between missense and truncating mutation carriers. Fernet M British journal of cancer 2004 PMID: 14970866
Independent mutational events are rare in the ATM gene: haplotype prescreening enhances mutation detection rate. Mitui M Human mutation 2003 PMID: 12815592
ATM mutations in patients with ataxia telangiectasia screened by a hierarchical strategy. Sasaki T Human mutation 1998 PMID: 9711876

Text-mined citations for rs377349459...

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These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Nov 28, 2021