NM_000051.3(ATM):c.7988T>C (p.Val2663Ala) AND not specified

Clinical significance:Uncertain significance (Last evaluated: Nov 24, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000120160.6

Allele description [Variation Report for NM_000051.3(ATM):c.7988T>C (p.Val2663Ala)]

NM_000051.3(ATM):c.7988T>C (p.Val2663Ala)

Genes:
ATM:ATM serine/threonine kinase [Gene - OMIM - HGNC]
C11orf65:chromosome 11 open reading frame 65 [Gene - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
11q22.3
Genomic location:
Preferred name:
NM_000051.3(ATM):c.7988T>C (p.Val2663Ala)
Other names:
p.V2663A:GTT>GCT
HGVS:
  • NC_000011.10:g.108333946T>C
  • NG_009830.1:g.116115T>C
  • NG_054724.1:g.140887A>G
  • NM_000051.3:c.7988T>C
  • NM_001330368.2:c.641-24875A>G
  • NM_001351110.2:c.38+1274A>G
  • NM_001351834.2:c.7988T>C
  • NP_000042.3:p.Val2663Ala
  • NP_001338763.1:p.Val2663Ala
  • LRG_135t1:c.7988T>C
  • LRG_135:g.116115T>C
  • LRG_135p1:p.Val2663Ala
  • NC_000011.9:g.108204673T>C
Protein change:
V2663A
Links:
dbSNP: rs377648506
NCBI 1000 Genomes Browser:
rs377648506
Molecular consequence:
  • NM_001330368.2:c.641-24875A>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001351110.2:c.38+1274A>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000051.3:c.7988T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001351834.2:c.7988T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000084302ITMIno assertion providednot providedgermlinereference population

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

SCV000916554Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
Uncertain significance
(Nov 24, 2020)
germlineclinical testing

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

Citation Link

Description

Please see associated publication for description of ethnicities

SCV000084302

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing
Africangermlineunknownnot providednot providednot provided43not providedreference population
African_Europeangermlineunknownnot providednot providednot provided46not providedreference population
Central_Asiangermlineunknownnot providednot providednot provided50not providedreference population
East_Asiangermlineunknownnot providednot providednot provided62not providedreference population
Europeangermlineunknownnot providednot providednot provided331not providedreference population
Hispanicgermlineunknownnot providednot providednot provided118not providedreference population
Whole_cohortgermlineunknownnot providednot providednot provided681not providedreference population

Citations

PubMed

Germline variation in cancer-susceptibility genes in a healthy, ancestrally diverse cohort: implications for individual genome sequencing.

Bodian DL, McCutcheon JN, Kothiyal P, Huddleston KC, Iyer RK, Vockley JG, Niederhuber JE.

PLoS One. 2014;9(4):e94554. doi: 10.1371/journal.pone.0094554.

PubMed [citation]
PMID:
24728327
PMCID:
PMC3984285

Frequency of Germline Mutations in 25 Cancer Susceptibility Genes in a Sequential Series of Patients With Breast Cancer.

Tung N, Lin NU, Kidd J, Allen BA, Singh N, Wenstrup RJ, Hartman AR, Winer EP, Garber JE.

J Clin Oncol. 2016 May 1;34(13):1460-8. doi: 10.1200/JCO.2015.65.0747. Epub 2016 Mar 14.

PubMed [citation]
PMID:
26976419
PMCID:
PMC4872307

Details of each submission

From ITMI, SCV000084302.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1Africannot providednot providednot providedreference population PubMed (1)
2African_Europeannot providednot providednot providedreference population PubMed (1)
3Central_Asiannot providednot providednot providedreference population PubMed (1)
4East_Asiannot providednot providednot providedreference population PubMed (1)
5Europeannot providednot providednot providedreference population PubMed (1)
6Hispanicnot providednot providednot providedreference population PubMed (1)
7Whole_cohortnot providednot providednot providedreference population PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknown43not provideddiscoverynot provided0not providednot provided
2germlineunknown46not provideddiscoverynot provided0.0122not providednot provided
3germlineunknown50not provideddiscoverynot provided0not providednot provided
4germlineunknown62not provideddiscoverynot provided0not providednot provided
5germlineunknown331not provideddiscoverynot provided0not providednot provided
6germlineunknown118not provideddiscoverynot provided0not providednot provided
7germlineunknown681not provideddiscoverynot provided0.0008not providednot provided

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000916554.2

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

Description

Variant summary: ATM c.7988T>C (p.Val2663Ala) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 5.6e-05 in 251198 control chromosomes. This frequency is not significantly higher than expected for a pathogenic variant in ATM causing Ataxia Telangiectasia or Breast Cancer, allowing no conclusion about variant significance. c.7988T>C has been reported in the literature in at-least one individual affected with Breast Cancer (Tung_2016). This report does not provide unequivocal conclusions about association of the variant with Ataxia Telangiectasia or Breast Cancer. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. 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: Jun 14, 2021

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