ClinVar Genomic variation as it relates to human health
NM_000051.4(ATM):c.7985T>A (p.Val2662Asp)
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.7985T>A (p.Val2662Asp)
Variation ID: 216025 Accession: VCV000216025.17
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 11q22.3 11: 108333943 (GRCh38) [ NCBI UCSC ] 11: 108204670 (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 Dec 26, 2017 Feb 20, 2024 Feb 8, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000051.4:c.7985T>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000042.3:p.Val2662Asp missense NM_001330368.2:c.641-24872A>T intron variant NM_001351110.2:c.*38+1277A>T intron variant NM_001351834.2:c.7985T>A NP_001338763.1:p.Val2662Asp missense NC_000011.10:g.108333943T>A NC_000011.9:g.108204670T>A NG_009830.1:g.116112T>A NG_054724.1:g.140890A>T LRG_135:g.116112T>A LRG_135t1:c.7985T>A LRG_135p1:p.Val2662Asp - Protein change
- V2662D
- Other names
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- Canonical SPDI
- NC_000011.10:108333942:T:A
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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.
Trans-Omics for Precision Medicine (TOPMed) 0.00002
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
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
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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 |
10007 | 16113 | |
C11orf65 | - | - | - |
GRCh38 GRCh37 |
3 | 6090 |
Conditions - Germline
Condition
Help
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
Help
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/Likely pathogenic (4) |
criteria provided, multiple submitters, no conflicts
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Dec 12, 2022 | RCV000200768.21 | |
Pathogenic/Likely pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Sep 8, 2021 | RCV001176540.11 | |
Pathogenic (1) |
criteria provided, single submitter
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Feb 8, 2023 | RCV003468895.1 |
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
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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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Likely pathogenic
(Jan 22, 2018)
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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: SCV000797315.1
First in ClinVar: Dec 26, 2017 Last updated: Dec 26, 2017 |
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Pathogenic
(Jun 03, 2021)
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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: SCV001737760.1
First in ClinVar: Jun 23, 2021 Last updated: Jun 23, 2021 |
Comment:
Variant summary: ATM c.7985T>A (p.Val2662Asp) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging … (more)
Variant summary: ATM c.7985T>A (p.Val2662Asp) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251228 control chromosomes. c.7985T>A has been reported in the literature in multiple individuals affected with Ataxia-Telangiectasia (Jacquemin_2012, Landoure_2013). These data indicate that the variant is very likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function. These results showed that ATM-V2662D had decreased expression level, mislocalization to cytoplasm, and decreased phosphorylation of ATM target proteins (Jacquemin_2012, Fievet_2018). Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation (pathogenic/likely pathogenic n=2, VUS n=1). Based on the evidence outlined above, the variant was classified as pathogenic. (less)
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Pathogenic
(Oct 29, 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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Ambry Genetics
Accession: SCV002678061.1
First in ClinVar: Nov 29, 2022 Last updated: Nov 29, 2022 |
Comment:
The p.V2662D pathogenic mutation (also known as c.7985T>A), located in coding exon 53 of the ATM gene, results from a T to A substitution at … (more)
The p.V2662D pathogenic mutation (also known as c.7985T>A), located in coding exon 53 of the ATM gene, results from a T to A substitution at nucleotide position 7985. The valine at codon 2662 is replaced by aspartic acid, an amino acid with highly dissimilar properties. This alteration has been seen in the homozygous state in multiple individuals diagnosed with ataxia-telangiectasia, including three out of three affected siblings in one consanguineous family (Jacquemin V et al. Eur. J. Hum. Genet. 2012 Mar;20:305-12; Landouré G et al. J. Neurol. 2013 Jan;260:324-6; Jeddane L et al. Neuromolecular Med. 2013 Jun;15:288-94). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation. (less)
Number of individuals with the variant: 1
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Pathogenic
(Feb 08, 2023)
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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: SCV004212097.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
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Pathogenic
(May 14, 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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Revvity Omics, Revvity
Accession: SCV002022366.3
First in ClinVar: Nov 29, 2021 Last updated: Feb 04, 2024 |
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Likely pathogenic
(Sep 08, 2021)
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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: SCV004361874.1
First in ClinVar: Feb 14, 2024 Last updated: Feb 14, 2024 |
Comment:
This missense variant replaces valine with aspartic acid at codon 2662 of the ATM protein. Computational prediction suggests that this variant may have deleterious impact … (more)
This missense variant replaces valine with aspartic acid at codon 2662 of the ATM protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). This variant has been reported in the homozygous state in multiple individuals affected with ataxia telangiectasia (PMID: 22071889, 22109722, 23142947, 23322442, 27066513, 31050087). Cells derived from these individuals showed decreased nuclear ATM protein level and decreased phosphorylation of CHK2 and KAP1 (PMID: 22071889, 31050087). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Based on the available evidence, this variant is classified as Likely Pathogenic. (less)
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Pathogenic
(Dec 12, 2022)
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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: SCV000253747.8
First in ClinVar: Oct 11, 2015 Last updated: Feb 20, 2024 |
Comment:
For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects ATM function (PMID: 22071889). Algorithms developed … (more)
For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects ATM function (PMID: 22071889). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 216025). This missense change has been observed in individuals with ataxia telangiectasia (PMID: 22071889, 23142947, 23322442). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces valine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 2662 of the ATM protein (p.Val2662Asp). (less)
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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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Functional classification of ATM variants in ataxia-telangiectasia patients. | Fiévet A | Human mutation | 2019 | PMID: 31050087 |
Genetics and genomic medicine in Mali: challenges and future perspectives. | Landouré G | Molecular genetics & genomic medicine | 2016 | PMID: 27066513 |
Molecular defects in Moroccan patients with ataxia-telangiectasia. | Jeddane L | Neuromolecular medicine | 2013 | PMID: 23322442 |
Novel mutation in the ATM gene in a Malian family with ataxia telangiectasia. | Landouré G | Journal of neurology | 2013 | PMID: 23142947 |
Underexpression and abnormal localization of ATM products in ataxia telangiectasia patients bearing ATM missense mutations. | Jacquemin V | European journal of human genetics : EJHG | 2012 | PMID: 22071889 |
Genetic testing and counseling for hereditary neurological diseases in Mali. | Meilleur KG | Journal of community genetics | 2011 | PMID: 22109722 |
Text-mined citations for rs863224463 ...
HelpRecord last updated Apr 20, 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.