NM_000051.4(ATM):c.4396C>G (p.Arg1466Gly) AND Ataxia-telangiectasia syndrome

Clinical significance:Uncertain significance (Last evaluated: Nov 12, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000197917.6

Allele description [Variation Report for NM_000051.4(ATM):c.4396C>G (p.Arg1466Gly)]

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

Gene:
ATM:ATM serine/threonine kinase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
11q22.3
Genomic location:
Preferred name:
NM_000051.4(ATM):c.4396C>G (p.Arg1466Gly)
Other names:
p.R1466G:CGA>GGA
HGVS:
  • NC_000011.10:g.108289761C>G
  • NG_009830.1:g.71930C>G
  • NM_000051.4:c.4396C>GMANE SELECT
  • NM_001351834.2:c.4396C>G
  • NP_000042.3:p.Arg1466Gly
  • NP_000042.3:p.Arg1466Gly
  • NP_001338763.1:p.Arg1466Gly
  • LRG_135t1:c.4396C>G
  • LRG_135:g.71930C>G
  • LRG_135p1:p.Arg1466Gly
  • NC_000011.9:g.108160488C>G
  • NM_000051.3:c.4396C>G
  • p.R1466G
Protein change:
R1466G
Links:
dbSNP: rs730881369
NCBI 1000 Genomes Browser:
rs730881369
Molecular consequence:
  • NM_000051.4:c.4396C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001351834.2:c.4396C>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Ataxia-telangiectasia syndrome (AT)
Synonyms:
Louis-Bar syndrome; Cerebello-oculocutaneous telangiectasia; Immunodeficiency with ataxia telangiectasia; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0008840; MedGen: C0004135; Orphanet: 100; OMIM: 208900

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000254106Invitaecriteria provided, single submitter
Uncertain significance
(Nov 12, 2019)
germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV000254106.7

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

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 moderate physicochemical difference between arginine and glycine. This variant is present in population databases (rs730881369, ExAC 0.002%). This variant has not been reported in the literature in individuals with ATM-related disease. ClinVar contains an entry for this variant (Variation ID: 181956). 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, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Dec 4, 2021

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