NM_000051.4(ATM):c.5618G>A (p.Cys1873Tyr) AND Ataxia-telangiectasia syndrome

Clinical significance:Uncertain significance (Last evaluated: Dec 11, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000627966.4

Allele description [Variation Report for NM_000051.4(ATM):c.5618G>A (p.Cys1873Tyr)]

NM_000051.4(ATM):c.5618G>A (p.Cys1873Tyr)

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.5618G>A (p.Cys1873Tyr)
HGVS:
  • NC_000011.10:g.108304796G>A
  • NG_009830.1:g.86965G>A
  • NM_000051.3:c.5618G>A
  • NM_000051.4:c.5618G>AMANE SELECT
  • NM_001351834.2:c.5618G>A
  • NP_000042.3:p.Cys1873Tyr
  • NP_000042.3:p.Cys1873Tyr
  • NP_001338763.1:p.Cys1873Tyr
  • LRG_135t1:c.5618G>A
  • LRG_135:g.86965G>A
  • LRG_135p1:p.Cys1873Tyr
  • NC_000011.9:g.108175523G>A
Protein change:
C1873Y
Links:
dbSNP: rs587782239
NCBI 1000 Genomes Browser:
rs587782239
Molecular consequence:
  • NM_000051.3:c.5618G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_000051.4:c.5618G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001351834.2:c.5618G>A - 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
SCV000748852Invitaecriteria provided, single submitter
Uncertain significance
(Dec 11, 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, SCV000748852.4

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

Description

This sequence change replaces cysteine with tyrosine at codon 1873 of the ATM protein (p.Cys1873Tyr). The cysteine residue is moderately conserved and there is a large physicochemical difference between cysteine and tyrosine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with an ATM-related disease. ClinVar contains an entry for this variant (Variation ID: 233138). 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 tolerated, but these predictions have not been confirmed by published functional studies. In summary, this variant is a rare missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. 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: Oct 25, 2021

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