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NM_000051.4(ATM):c.6115G>A (p.Glu2039Lys) AND Ataxia-telangiectasia syndrome

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Nov 21, 2023
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
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:
RCV000204272.16

Allele description [Variation Report for NM_000051.4(ATM):c.6115G>A (p.Glu2039Lys)]

NM_000051.4(ATM):c.6115G>A (p.Glu2039Lys)

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_000051.4(ATM):c.6115G>A (p.Glu2039Lys)
HGVS:
  • NC_000011.10:g.108316030G>A
  • NG_009830.1:g.98199G>A
  • NG_054724.1:g.158803C>T
  • NM_000051.4:c.6115G>AMANE SELECT
  • NM_001330368.2:c.641-6959C>T
  • NM_001351110.2:c.*39-6959C>T
  • NM_001351834.2:c.6115G>A
  • NP_000042.3:p.Glu2039Lys
  • NP_000042.3:p.Glu2039Lys
  • NP_001338763.1:p.Glu2039Lys
  • LRG_135t1:c.6115G>A
  • LRG_135:g.98199G>A
  • LRG_135p1:p.Glu2039Lys
  • NC_000011.9:g.108186757G>A
  • NM_000051.3:c.6115G>A
Protein change:
E2039K
Links:
dbSNP: rs864622251
NCBI 1000 Genomes Browser:
rs864622251
Molecular consequence:
  • NM_001330368.2:c.641-6959C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001351110.2:c.*39-6959C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000051.4:c.6115G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001351834.2:c.6115G>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
SCV000259858Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Pathogenic
(Nov 21, 2023)
germlineclinical testing

PubMed (7)
[See all records that cite these PMIDs]

Summary from all submissions

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

Citations

PubMed

Rare, evolutionarily unlikely missense substitutions in ATM confer increased risk of breast cancer.

Tavtigian SV, Oefner PJ, Babikyan D, Hartmann A, Healey S, Le Calvez-Kelm F, Lesueur F, Byrnes GB, Chuang SC, Forey N, Feuchtinger C, Gioia L, Hall J, Hashibe M, Herte B, McKay-Chopin S, Thomas A, Vallée MP, Voegele C, Webb PM, Whiteman DC; Australian Cancer Study.; et al.

Am J Hum Genet. 2009 Oct;85(4):427-46. doi: 10.1016/j.ajhg.2009.08.018. Epub 2009 Sep 24.

PubMed [citation]
PMID:
19781682
PMCID:
PMC2756555

Longitudinal analysis of the neurological features of ataxia-telangiectasia.

Jackson TJ, Chow G, Suri M, Byrd P, Taylor MR, Whitehouse WP.

Dev Med Child Neurol. 2016 Jul;58(7):690-7. doi: 10.1111/dmcn.13052. Epub 2016 Feb 19.

PubMed [citation]
PMID:
26896183
See all PubMed Citations (7)

Details of each submission

From Invitae, SCV000259858.7

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (7)

Description

This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 2039 of the ATM protein (p.Glu2039Lys). This variant is present in population databases (no rsID available, gnomAD 0.003%). This missense change has been observed in individuals with ataxia-telangiectasia and/or breast cancer (PMID: 19781682, 22071889, 26896183, 30303537, 30549301; Invitae). ClinVar contains an entry for this variant (Variation ID: 219787). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. Experimental studies have shown that this missense change affects ATM function (PMID: 19431188, 22071889). For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: Jul 15, 2024