ClinVar Genomic variation as it relates to human health
NM_000051.4(ATM):c.7202T>C (p.Ile2401Thr)
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.7202T>C (p.Ile2401Thr)
Variation ID: 453666 Accession: VCV000453666.28
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 11q22.3 11: 108329133 (GRCh38) [ NCBI UCSC ] 11: 108199860 (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 May 1, 2024 Oct 3, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000051.4:c.7202T>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000042.3:p.Ile2401Thr missense NM_001330368.2:c.641-20062A>G intron variant NM_001351110.2:c.*38+6087A>G intron variant NM_001351834.2:c.7202T>C NP_001338763.1:p.Ile2401Thr missense NC_000011.10:g.108329133T>C NC_000011.9:g.108199860T>C NG_009830.1:g.111302T>C NG_054724.1:g.145700A>G LRG_135:g.111302T>C LRG_135t1:c.7202T>C LRG_135p1:p.Ile2401Thr - Protein change
- I2401T
- Other names
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- Canonical SPDI
- NC_000011.10:108329132:T:C
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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
Help
The frequency of the allele represented by this VCV record.
Trans-Omics for Precision Medicine (TOPMed) 0.00000
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
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
Help
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
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 |
10314 | 16610 | |
C11orf65 | - | - | - |
GRCh38 GRCh37 |
3 | 6280 |
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
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
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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Uncertain significance (3) |
criteria provided, multiple submitters, no conflicts
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Oct 3, 2023 | RCV000549388.17 | |
Uncertain significance (3) |
criteria provided, multiple submitters, no conflicts
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May 18, 2023 | RCV000777216.15 | |
Uncertain significance (1) |
criteria provided, single submitter
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May 31, 2023 | RCV003470681.1 |
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
Help
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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Uncertain significance
(Sep 11, 2018)
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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: SCV000912907.1
First in ClinVar: May 20, 2019 Last updated: May 20, 2019 |
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Uncertain significance
(May 28, 2019)
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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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Mendelics
Accession: SCV001138558.1
First in ClinVar: Jan 09, 2020 Last updated: Jan 09, 2020 |
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Uncertain significance
(Feb 26, 2022)
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criteria provided, single submitter
Method: curation
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Sema4, Sema4
Accession: SCV002537042.1
First in ClinVar: Jun 24, 2022 Last updated: Jun 24, 2022
Comment:
The ATM c.7202T>C (p.I2401T) has been reported in at least 2 individuals with breast cancer (PMID 12810666, 19781682, 34204722). It has also been reported in … (more)
The ATM c.7202T>C (p.I2401T) has been reported in at least 2 individuals with breast cancer (PMID 12810666, 19781682, 34204722). It has also been reported in 1 woman with breast cancer in a large dataset of 60,466 women with breast cancer and 53,461 controls (PMID 33471991). This variant is not reported in the population database Genome Aggregation Database (http://gnomad.broadinstitute.org, PMID 32461654). This variant has been reported in ClinVar (Variation ID 453666). In silico tools suggest the impact of the variant on protein function is deleterious, though these predictions have not been confirmed by functional studies. The evidence is insufficient to meet ACMG/AMP criteria for classifying the variant as benign or pathogenic. Thus, the clinical significance of this variant is currently uncertain. (less)
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Uncertain significance
(May 31, 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: SCV004210329.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
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Uncertain significance
(Oct 03, 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: SCV000622723.6
First in ClinVar: Dec 26, 2017 Last updated: Feb 20, 2024 |
Comment:
This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 2401 of the ATM protein (p.Ile2401Thr). … (more)
This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 2401 of the ATM protein (p.Ile2401Thr). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with breast and/or ovarian cancer (PMID: 12810666, 19781682). ClinVar contains an entry for this variant (Variation ID: 453666). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. (less)
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Uncertain significance
(May 18, 2023)
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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: SCV001188480.5
First in ClinVar: Mar 16, 2020 Last updated: May 01, 2024 |
Comment:
The p.I2401T variant (also known as c.7202T>C), located in coding exon 48 of the ATM gene, results from a T to C substitution at nucleotide … (more)
The p.I2401T variant (also known as c.7202T>C), located in coding exon 48 of the ATM gene, results from a T to C substitution at nucleotide position 7202. The isoleucine at codon 2401 is replaced by threonine, an amino acid with similar properties. This variant was seen in one breast cancer case in a case-control study (Tavtigian SV et al. Am. J. Hum. Genet., 2009 Oct;85:427-46). This alteration was also identified in 1 of 7636 unselected prostate cancer patients and 0 of 12366 male controls of Japanese ancestry (Momozawa Y et al. J Natl Cancer Inst, 2020 Apr;112:369-376). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. (less)
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Uncertain significance
(Dec 04, 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: SCV002078130.1
First in ClinVar: Apr 23, 2022 Last updated: Apr 23, 2022 |
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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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Prevalence and Clinicopathological Characteristics of Moderate and High-Penetrance Genes in Non-BRCA1/2 Breast Cancer High-Risk Spanish Families. | Fonfria M | Journal of personalized medicine | 2021 | PMID: 34204722 |
Breast Cancer Risk Genes - Association Analysis in More than 113,000 Women. | Breast Cancer Association Consortium | The New England journal of medicine | 2021 | PMID: 33471991 |
Germline Pathogenic Variants in 7636 Japanese Patients With Prostate Cancer and 12 366 Controls. | Momozawa Y | Journal of the National Cancer Institute | 2020 | PMID: 31214711 |
Discovering moderate-risk breast cancer susceptibility genes. | Hollestelle A | Current opinion in genetics & development | 2010 | PMID: 20346647 |
Rare, evolutionarily unlikely missense substitutions in ATM confer increased risk of breast cancer. | Tavtigian SV | American journal of human genetics | 2009 | PMID: 19781682 |
Contributions of ATM mutations to familial breast and ovarian cancer. | Thorstenson YR | Cancer research | 2003 | PMID: 12810666 |
Text-mined citations for rs1555122117 ...
HelpRecord last updated May 08, 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.