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NM_000051.4(ATM):c.2074C>T (p.Arg692Cys)

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Interpretation:
Conflicting interpretations of pathogenicity​

Likely benign(1);Uncertain significance(4)

Review status:
criteria provided, conflicting interpretations
Submissions:
5 (Most recent: Jun 22, 2021)
Last evaluated:
Oct 19, 2020
Accession:
VCV000184752.11
Variation ID:
184752
Description:
single nucleotide variant
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NM_000051.4(ATM):c.2074C>T (p.Arg692Cys)

Allele ID
183174
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
11q22.3
Genomic location
11: 108253989 (GRCh38) GRCh38 UCSC
11: 108124716 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000011.9:g.108124716C>T
NM_000051.3:c.2074C>T NP_000042.3:p.Arg692Cys missense
NC_000011.10:g.108253989C>T
... more HGVS
Protein change
R692C
Other names
-
Canonical SPDI
NC_000011.10:108253988:C:T
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
Exome Aggregation Consortium (ExAC) 0.00001
Trans-Omics for Precision Medicine (TOPMed) 0.00002
The Genome Aggregation Database (gnomAD), exomes 0.00001
Links
ClinGen: CA189945
dbSNP: rs765965513
VarSome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Uncertain significance 1 criteria provided, single submitter Oct 19, 2020 RCV000168071.8
Uncertain significance 1 criteria provided, single submitter Jun 5, 2019 RCV000219263.3
Uncertain significance 1 criteria provided, single submitter Apr 6, 2018 RCV000780902.1
Conflicting interpretations of pathogenicity 2 criteria provided, conflicting interpretations Mar 23, 2020 RCV000164063.5
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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

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Likely benign
(Aug 28, 2018)
criteria provided, single submitter
Method: clinical testing
Hereditary cancer-predisposing syndrome
Allele origin: germline
Ambry Genetics
Accession: SCV000214673.5
Submitted: (Nov 30, 2020)
Evidence details
Publications
PubMed (1)
Comment:
In silico models in agreement (benign);Other strong data supporting benign classification
Uncertain significance
(Oct 19, 2020)
criteria provided, single submitter
Method: clinical testing
Ataxia-telangiectasia syndrome
Allele origin: germline
Invitae
Accession: SCV000218725.9
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (3)
Comment:
This sequence change replaces arginine with cysteine at codon 692 of the ATM protein (p.Arg692Cys). The arginine residue is weakly conserved and there is a … (more)
Uncertain significance
(Jun 05, 2019)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV000278813.11
Submitted: (Jun 22, 2021)
Evidence details
Comment:
Not observed at a significant frequency in large population cohorts (Lek et al., 2016) In silico analysis, which includes protein predictors and evolutionary conservation, supports … (more)
Uncertain significance
(Apr 06, 2018)
criteria provided, single submitter
Method: clinical testing
not specified
Allele origin: germline
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000918538.1
Submitted: (Apr 24, 2019)
Evidence details
Publications
PubMed (3)
Comment:
Variant summary: ATM c.2074C>T (p.Arg692Cys) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign … (more)
Uncertain significance
(Mar 23, 2020)
criteria provided, single submitter
Method: clinical testing
Hereditary cancer-predisposing syndrome
Allele origin: germline
Color Health, Inc
Accession: SCV000911566.2
Submitted: (May 19, 2020)
Comment:
This missense variant replaces arginine with cysteine at codon 692 of the ATM protein. Computational prediction suggests that this variant may not impact protein structure … (more)
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
Rare, protein-truncating variants in <i>ATM</i>, <i>CHEK2</i> and <i>PALB2</i>, but not <i>XRCC2</i>, are associated with increased breast cancer risks. Decker B Journal of medical genetics 2017 PMID: 28779002
Rare germline variants in ATM are associated with chronic lymphocytic leukemia. Tiao G Leukemia 2017 PMID: 28652578
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
Prioritizing Variants in Complete Hereditary Breast and Ovarian Cancer Genes in Patients Lacking Known BRCA Mutations. Caminsky NG Human mutation 2016 PMID: 26898890

Text-mined citations for rs765965513...

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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 Oct 30, 2021