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NM_000051.3(ATM):c.8147T>C (p.Val2716Ala) AND Ataxia-telangiectasia syndrome

Germline classification:
Pathogenic/Likely pathogenic (3 submissions)
Last evaluated:
Nov 30, 2017
Review status:
2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV000169105.5

Allele description

NM_000051.3(ATM):c.8147T>C (p.Val2716Ala)

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.8147T>C (p.Val2716Ala)
Other names:
p.V2716A:GTT>GCT
HGVS:
  • NC_000011.10:g.108335105T>C
  • NG_009830.1:g.117274T>C
  • NM_000051.3:c.8147T>C
  • NP_000042.3:p.Val2716Ala
  • LRG_135t1:c.8147T>C
  • LRG_135:g.117274T>C
  • LRG_135p1:p.Val2716Ala
  • NC_000011.9:g.108205832T>C
  • p.V2716A
Protein change:
V2716A
Links:
dbSNP: rs587782652
NCBI 1000 Genomes Browser:
rs587782652
Allele Frequency:
0.00004(C)
Molecular consequence:
  • NM_000051.3:c.8147T>C - 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:
MedGen: C0004135; Orphanet: 100; OMIM: 208900

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000220304Counsyl
criteria provided, single submitter

(Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015))
Likely pathogenic
(May 13, 2014)
unknownliterature only

PubMed (5)
[See all records that cite these PMIDs]

Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015),

Citation Link,

SCV000260088Invitae
criteria provided, single submitter

(Nykamp K et al. (Genet Med 2017))
Pathogenic
(Nov 30, 2017)
germlineclinical testing

PubMed (9)
[See all records that cite these PMIDs]

SCV000328271GeneReviews
no assertion criteria provided
Pathogenic
(Oct 27, 2016)
germlineliterature only

PubMed (2)
[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
not providedgermlineyesnot providednot providednot providednot providednot providedliterature only
not providedunknownunknownnot providednot providednot providednot providednot providedliterature only

Citations

PubMed

Functional consequences of sequence alterations in the ATM gene.

Lavin MF, Scott S, Gueven N, Kozlov S, Peng C, Chen P.

DNA Repair (Amst). 2004 Aug-Sep;3(8-9):1197-205. Review.

PubMed [citation]
PMID:
15279808

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
See all PubMed Citations (11)

Details of each submission

From Counsyl, SCV000220304.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (5)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

From Invitae, SCV000260088.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (9)

Description

This sequence change replaces valine with alanine at codon 2716 of the ATM protein (p.Val2716Ala). The valine residue is highly conserved and there is a small physicochemical difference between valine and alanine. This variant is present in population databases (rs587782652, ExAC 0.02%). This variant has been reported in several individuals affected with ataxia-telangiectasia (A-T) (PMID: 16864838, 19535770, 21354641, 21965147), as well as in an individual with generalized dystonia (PMID: 2557216), and an individual with breast cancer (PMID: 26976419). This variant has been reported to segregate with another pathogenic variant in ATM in a single family with dystonia (PMID: 25957637). ClinVar contains an entry for this variant (Variation ID: 142700). Experimental studies have shown that this missense change reduces ATM kinase activity and increases radiosensitivity (PMID: 11805335). For these reasons, this variant has been classified as Pathogenic.

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

From GeneReviews, SCV000328271.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (2)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Aug 24, 2018