ClinVar Genomic variation as it relates to human health
NM_000051.4(ATM):c.5692C>T (p.Arg1898Ter)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000051.4(ATM):c.5692C>T (p.Arg1898Ter)
Variation ID: 482526 Accession: VCV000482526.47
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 11q22.3 11: 108307914 (GRCh38) [ NCBI UCSC ] 11: 108178641 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Feb 19, 2018 Jun 17, 2024 Jan 25, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000051.4:c.5692C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000042.3:p.Arg1898Ter nonsense NM_001351834.2:c.5692C>T NP_001338763.1:p.Arg1898Ter nonsense NC_000011.10:g.108307914C>T NC_000011.9:g.108178641C>T NG_009830.1:g.90083C>T NG_054724.1:g.166919G>A LRG_135:g.90083C>T LRG_135t1:c.5692C>T LRG_135p1:p.Arg1898Ter - Protein change
- R1898*
- Other names
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- Canonical SPDI
- NC_000011.10:108307913:C:T
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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Allele frequency
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The frequency of the allele represented by this VCV record.
Exome Aggregation Consortium (ExAC) 0.00001
The Genome Aggregation Database (gnomAD), exomes 0.00001
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
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Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
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The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
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The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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ATM | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
10341 | 16658 |
Conditions - Germline
Condition
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The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
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The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Sep 13, 2022 | RCV000571941.8 | |
Pathogenic (5) |
criteria provided, multiple submitters, no conflicts
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Dec 11, 2023 | RCV000671308.20 | |
Pathogenic (1) |
no assertion criteria provided
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- | RCV003332201.1 | |
Pathogenic (1) |
no assertion criteria provided
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Jul 1, 2021 | RCV003159965.2 | |
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Jan 25, 2024 | RCV003465216.3 | |
Pathogenic (1) |
criteria provided, single submitter
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Jun 16, 2022 | RCV002255463.3 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
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The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Pathogenic
(Sep 13, 2022)
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criteria provided, single submitter
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV000667807.5
First in ClinVar: Jan 01, 2018 Last updated: May 01, 2024 |
Comment:
The p.R1898* pathogenic mutation (also known as c.5692C>T), located in coding exon 37 of the ATM gene, results from a C to T substitution at … (more)
The p.R1898* pathogenic mutation (also known as c.5692C>T), located in coding exon 37 of the ATM gene, results from a C to T substitution at nucleotide position 5692. This changes the amino acid from an arginine to a stop codon within coding exon 37. This pathogenic mutation has been reported in the literature in conjunction with other ATM mutations in multiple individuals with ataxia telangiectasia (Magliozzi M et al. Dis. Markers 2006; 22(4):257-64; Jeddane L et al. Neuromolecular Med. 2013 Jun;15(2):288-94; Nespoli L et al. Case Reports Immunol 2013;2013:296827.doi:10.1155/2013/296827; Nakamura K et al. Mol Genet Genomic Med 2014 Jul;2(4):332-40). 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. (less)
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Pathogenic
(Jan 15, 2020)
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criteria provided, single submitter
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Color Diagnostics, LLC DBA Color Health
Accession: SCV000687636.3
First in ClinVar: Feb 19, 2018 Last updated: Jan 12, 2022 |
Comment:
This variant changes 1 nucleotide in exon 38 of the ATM gene, creating a premature translation stop signal. This variant is expected to result in … (more)
This variant changes 1 nucleotide in exon 38 of the ATM gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been identified in 2/251006 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Loss of ATM function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic. (less)
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Pathogenic
(Dec 08, 2017)
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criteria provided, single submitter
Method: clinical testing
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Ataxia-telangiectasia syndrome
Affected status: unknown
Allele origin:
unknown
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Counsyl
Accession: SCV000796269.1
First in ClinVar: Aug 05, 2018 Last updated: Aug 05, 2018 |
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Pathogenic
(May 22, 2019)
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criteria provided, single submitter
Method: clinical testing
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Ataxia-telangiectasia syndrome
Affected status: unknown
Allele origin:
germline
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ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV001158445.1
First in ClinVar: Feb 10, 2020 Last updated: Feb 10, 2020 |
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Pathogenic
(Dec 11, 2023)
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criteria provided, single submitter
Method: clinical testing
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Ataxia-telangiectasia syndrome
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000956854.7
First in ClinVar: Aug 14, 2019 Last updated: Feb 20, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Arg1898*) in the ATM gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Arg1898*) 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 present in population databases (rs775036118, gnomAD 0.003%). This premature translational stop signal has been observed in individual(s) with ataxia-telangiectasia and breast cancer (PMID: 17124347, 23322442, 23454770, 25077176, 25374739, 28724667). ClinVar contains an entry for this variant (Variation ID: 482526). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Jan 17, 2020)
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criteria provided, single submitter
Method: clinical testing
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Ataxia-telangiectasia syndrome
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV001337784.1
First in ClinVar: Jun 22, 2020 Last updated: Jun 22, 2020 |
Comment:
Variant summary: ATM c.5692C>T (p.Arg1898X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein … (more)
Variant summary: ATM c.5692C>T (p.Arg1898X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the 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. The variant allele was found at a frequency of 8e-06 in 251006 control chromosomes (gnomAD). c.5692C>T has been reported in the literature in multiple individuals affected with Breast Cancer or Ataxia-Telangiectasia (eg. Magliozzi_2006, Micol_2011, Nespoli_2013, Nakamura_2014, Momozawa_2018, Wang_2019). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Four ClinVar submitters (evaluation after 2014) cite the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic (less)
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Pathogenic
(Jun 16, 2022)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV002526531.2
First in ClinVar: Jun 24, 2022 Last updated: Mar 04, 2023 |
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 … (more)
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; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 25525159, 25374739, 17124347, 25077176, 23454770, 26896183, 29752822, 30287823, 27989354, 28724667, 30982232, 30607632, 23322442) (less)
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Pathogenic
(Jan 25, 2024)
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criteria provided, single submitter
Method: clinical testing
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Familial cancer of breast
Affected status: unknown
Allele origin:
unknown
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Myriad Genetics, Inc.
Accession: SCV004933539.1
First in ClinVar: May 01, 2024 Last updated: May 01, 2024 |
Comment:
This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation.
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Pathogenic
(Jan 22, 2024)
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criteria provided, single submitter
Method: clinical testing
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Familial cancer of breast
Affected status: unknown
Allele origin:
unknown
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Baylor Genetics
Accession: SCV004209513.2
First in ClinVar: Dec 30, 2023 Last updated: Jun 17, 2024 |
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Pathogenic
(Sep 16, 2020)
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no assertion criteria provided
Method: clinical testing
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Ataxia-telangiectasia
Affected status: unknown
Allele origin:
germline
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Natera, Inc.
Accession: SCV001452327.1
First in ClinVar: Jan 02, 2021 Last updated: Jan 02, 2021 |
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Pathogenic
(Jul 01, 2021)
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no assertion criteria provided
Method: research
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Gastric cancer
Affected status: unknown
Allele origin:
germline
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Laboratory for Genotyping Development, RIKEN
Accession: SCV002758100.1
First in ClinVar: Apr 15, 2023 Last updated: Apr 15, 2023 |
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Pathogenic
(-)
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no assertion criteria provided
Method: research
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Malignant tumor of urinary bladder
Affected status: yes
Allele origin:
somatic
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Laboratory of Urology, Hospital Clinic de Barcelona
Accession: SCV004040584.1
First in ClinVar: Oct 07, 2023 Last updated: Oct 07, 2023 |
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Germline Functional Evidence
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 germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Helicobacter pylori, Homologous-Recombination Genes, and Gastric Cancer. | Usui Y | The New England journal of medicine | 2023 | PMID: 36988593 |
Germline mutation landscape of Chinese patients with familial breast/ovarian cancer in a panel of 22 susceptibility genes. | Wang J | Cancer medicine | 2019 | PMID: 30982232 |
Germline pathogenic variants of 11 breast cancer genes in 7,051 Japanese patients and 11,241 controls. | Momozawa Y | Nature communications | 2018 | PMID: 30287823 |
Germline Mutations in Cancer Susceptibility Genes in a Large Series of Unselected Breast Cancer Patients. | Sun J | Clinical cancer research : an official journal of the American Association for Cancer Research | 2017 | PMID: 28724667 |
Ten new ATM alterations in Polish patients with ataxia-telangiectasia. | Podralska MJ | Molecular genetics & genomic medicine | 2014 | PMID: 25614872 |
A-TWinnipeg: Pathogenesis of rare ATM missense mutation c.6200C>A with decreased protein expression and downstream signaling, early-onset dystonia, cancer, and life-threatening radiotoxicity. | Nakamura K | Molecular genetics & genomic medicine | 2014 | PMID: 25077176 |
A precocious cerebellar ataxia and frequent Fever episodes in a 16-month-old infant revealing ataxia-telangiectasia syndrome. | Nespoli L | Case reports in immunology | 2013 | PMID: 25374739 |
Twelve novel Atm mutations identified in Chinese ataxia telangiectasia patients. | Huang Y | Neuromolecular medicine | 2013 | PMID: 23807571 |
p53 centrosomal localization diagnoses ataxia-telangiectasia homozygotes and heterozygotes. | Prodosmo A | The Journal of clinical investigation | 2013 | PMID: 23454770 |
Molecular defects in Moroccan patients with ataxia-telangiectasia. | Jeddane L | Neuromolecular medicine | 2013 | PMID: 23322442 |
Morbidity and mortality from ataxia-telangiectasia are associated with ATM genotype. | Micol R | The Journal of allergy and clinical immunology | 2011 | PMID: 21665257 |
DHPLC screening of ATM gene in Italian patients affected by ataxia-telangiectasia: fourteen novel ATM mutations. | Magliozzi M | Disease markers | 2006 | PMID: 17124347 |
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Text-mined citations for rs775036118 ...
HelpRecord last updated Jun 17, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.