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NM_000051.4(ATM):c.4396C>G (p.Arg1466Gly)

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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: Sep 14, 2021)
Last evaluated:
Jul 16, 2020
Accession:
VCV000181956.9
Variation ID:
181956
Description:
single nucleotide variant
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NM_000051.4(ATM):c.4396C>G (p.Arg1466Gly)

Allele ID
180458
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
11q22.3
Genomic location
11: 108289761 (GRCh38) GRCh38 UCSC
11: 108160488 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
LRG_135:g.71930C>G
LRG_135t1:c.4396C>G LRG_135p1:p.Arg1466Gly
NC_000011.10:g.108289761C>G
... more HGVS
Protein change
R1466G
Other names
p.R1466G:CGA>GGA
Canonical SPDI
NC_000011.10:108289760:C:G
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
Trans-Omics for Precision Medicine (TOPMed) 0.00001
The Genome Aggregation Database (gnomAD) 0.00003
Links
ClinGen: CA298242
dbSNP: rs730881369
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 Nov 12, 2019 RCV000197917.6
Uncertain significance 1 criteria provided, single submitter Aug 23, 2018 RCV000212014.3
Conflicting interpretations of pathogenicity 3 criteria provided, conflicting interpretations Jul 16, 2020 RCV000159723.9
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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
6424 10317

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Uncertain significance
(Aug 23, 2018)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV000209735.14
Submitted: (Jan 29, 2019)
Evidence details
Comment:
This variant is denoted ATM c.4396C>G at the cDNA level, p.Arg1466Gly (R1466G) at the protein level, and results in the change of an Arginine to … (more)
Uncertain significance
(Nov 12, 2019)
criteria provided, single submitter
Method: clinical testing
Ataxia-telangiectasia syndrome
Allele origin: germline
Invitae
Accession: SCV000254106.7
Submitted: (Feb 06, 2020)
Evidence details
Publications
PubMed (1)
Comment:
This sequence change replaces arginine with glycine at codon 1466 of the ATM protein (p.Arg1466Gly). The arginine residue is highly conserved and there is a … (more)
Likely benign
(Jul 16, 2020)
criteria provided, single submitter
Method: clinical testing
Hereditary cancer-predisposing syndrome
Allele origin: germline
Ambry Genetics
Accession: SCV000215787.5
Submitted: (Nov 30, 2020)
Evidence details
Comment:
Other strong data supporting benign classification
Uncertain significance
(Mar 01, 2019)
criteria provided, single submitter
Method: clinical testing
Hereditary cancer-predisposing syndrome
Allele origin: germline
Color Health, Inc
Accession: SCV000682202.3
Submitted: (May 19, 2020)
Evidence details
Uncertain significance
(Jun 17, 2020)
criteria provided, single submitter
Method: clinical testing
Hereditary cancer-predisposing syndrome
Allele origin: germline
Spanish ATM Cancer Susceptibility Variant Interpretation Working Group
Accession: SCV001911461.1
Submitted: (Sep 14, 2021)
Evidence details
Publications
PubMed (1)
Comment:
The c.4396C>G (p.Arg1466Gly) variant appears only twice in the gnomAD v2.1.1 non-cancer dataset (0.0007% frequency), specifically in the European (non-Finnish) subpopulation (PM2; http://gnomad.broadinstitute.org). This missense … (more)

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
A Collaborative Effort to Define Classification Criteria for ATM Variants in Hereditary Cancer Patients. Feliubadaló L Clinical chemistry 2021 PMID: 33280026
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

Text-mined citations for rs730881369...

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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 Dec 04, 2021