NM_000051.4(ATM):c.2887A>G (p.Met963Val) AND not specified

Clinical significance:Uncertain significance (Last evaluated: Feb 5, 2021)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001201309.1

Allele description [Variation Report for NM_000051.4(ATM):c.2887A>G (p.Met963Val)]

NM_000051.4(ATM):c.2887A>G (p.Met963Val)

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.2887A>G (p.Met963Val)
HGVS:
  • NC_000011.10:g.108271112A>G
  • NG_009830.1:g.53281A>G
  • NM_000051.4:c.2887A>GMANE SELECT
  • NM_001351834.2:c.2887A>G
  • NP_000042.3:p.Met963Val
  • NP_000042.3:p.Met963Val
  • NP_001338763.1:p.Met963Val
  • LRG_135t1:c.2887A>G
  • LRG_135:g.53281A>G
  • LRG_135p1:p.Met963Val
  • NC_000011.9:g.108141839A>G
  • NM_000051.3:c.2887A>G
  • p.M963V
Protein change:
M963V
Links:
dbSNP: rs374353016
NCBI 1000 Genomes Browser:
rs374353016
Molecular consequence:
  • NM_000051.4:c.2887A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001351834.2:c.2887A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001372448Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
Uncertain significance
(Feb 5, 2021)
germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Citation Link

Summary from all submissions

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

Citations

PubMed

Mutation Detection in Patients With Advanced Cancer by Universal Sequencing of Cancer-Related Genes in Tumor and Normal DNA vs Guideline-Based Germline Testing.

Mandelker D, Zhang L, Kemel Y, Stadler ZK, Joseph V, Zehir A, Pradhan N, Arnold A, Walsh MF, Li Y, Balakrishnan AR, Syed A, Prasad M, Nafa K, Carlo MI, Cadoo KA, Sheehan M, Fleischut MH, Salo-Mullen E, Trottier M, Lipkin SM, Lincoln A, et al.

JAMA. 2017 Sep 5;318(9):825-835. doi: 10.1001/jama.2017.11137. Erratum in: JAMA. 2018 Dec 11;320(22):2381.

PubMed [citation]
PMID:
28873162
PMCID:
PMC5611881

Unexpected cancer-predisposition gene variants in Cowden syndrome and Bannayan-Riley-Ruvalcaba syndrome patients without underlying germline PTEN mutations.

Yehia L, Ni Y, Sesock K, Niazi F, Fletcher B, Chen HJL, LaFramboise T, Eng C.

PLoS Genet. 2018 Apr;14(4):e1007352. doi: 10.1371/journal.pgen.1007352.

PubMed [citation]
PMID:
29684080
PMCID:
PMC5933810
See all PubMed Citations (4)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001372448.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

Variant summary: ATM c.2887A>G (p.Met963Val) results in a conservative amino acid change in the encoded protein sequence. Four of four in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 4e-05 in 298826 control chromosomes. This frequency is not significantly higher than expected for a pathogenic variant in ATM causing Ataxia-Telangiectasia (4e-05 vs 0.004), allowing no conclusion about variant significance. c.2887A>G has been reported in the literature in individuals affected with different types of cancer (Mandelker_2017, Yehia_2018, Bishop_2020, Fujita_2020). These reports do not provide unequivocal conclusions about association of the variant with Ataxia-Telangiectasia or breast cancer. Co-occurrence with a pathogenic variant has been reported (BRCA2 c.658_659delGT, p.Val220IlefsX4), providing supporting evidence for a benign role. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Six clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation (likely benign n=1, VUS n=5). Based on the evidence outlined above, the variant was classified as uncertain significance.

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

Last Updated: Dec 4, 2021

Support Center