NM_000051.4(ATM):c.3049C>T (p.Gln1017Ter) AND Ataxia-telangiectasia syndrome

Clinical significance:Pathogenic (Last evaluated: Sep 11, 2020)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000457084.7

Allele description [Variation Report for NM_000051.4(ATM):c.3049C>T (p.Gln1017Ter)]

NM_000051.4(ATM):c.3049C>T (p.Gln1017Ter)

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.3049C>T (p.Gln1017Ter)
Other names:
p.Q1017*:CAG>TAG
HGVS:
  • NC_000011.10:g.108271378C>T
  • NG_009830.1:g.53547C>T
  • NM_000051.4:c.3049C>TMANE SELECT
  • NM_001351834.2:c.3049C>T
  • NP_000042.3:p.Gln1017Ter
  • NP_000042.3:p.Gln1017Ter
  • NP_001338763.1:p.Gln1017Ter
  • LRG_135t1:c.3049C>T
  • LRG_135:g.53547C>T
  • LRG_135p1:p.Gln1017Ter
  • NC_000011.9:g.108142105C>T
  • NM_000051.3:c.3049C>T
  • p.Q1017*
Protein change:
Q1017*
Links:
dbSNP: rs730881388
NCBI 1000 Genomes Browser:
rs730881388
Molecular consequence:
  • NM_000051.4:c.3049C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001351834.2:c.3049C>T - nonsense - [Sequence Ontology: SO:0001587]

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
SCV000546762Invitaecriteria provided, single submitter
Pathogenic
(Sep 11, 2020)
germlineclinical testing

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

SCV000694246Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
Pathogenic
(Oct 28, 2019)
germlineclinical testing

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

Citation Link

Summary from all submissions

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

Citations

PubMed

Twelve novel Atm mutations identified in Chinese ataxia telangiectasia patients.

Huang Y, Yang L, Wang J, Yang F, Xiao Y, Xia R, Yuan X, Yan M.

Neuromolecular Med. 2013 Sep;15(3):536-40. doi: 10.1007/s12017-013-8240-3. Epub 2013 Jun 27. Erratum in: Neuromolecular Med. 2014 Mar;16(1):216.

PubMed [citation]
PMID:
23807571
PMCID:
PMC3732755

Ten new ATM alterations in Polish patients with ataxia-telangiectasia.

Podralska MJ, Stembalska A, Ślęzak R, Lewandowicz-Uszyńska A, Pietrucha B, Kołtan S, Wigowska-Sowińska J, Pilch J, Mosor M, Ziółkowska-Suchanek I, Dzikiewicz-Krawczyk A, Słomski R.

Mol Genet Genomic Med. 2014 Nov;2(6):504-11. doi: 10.1002/mgg3.98. Epub 2014 Jul 30.

PubMed [citation]
PMID:
25614872
PMCID:
PMC4303220
See all PubMed Citations (4)

Details of each submission

From Invitae, SCV000546762.7

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

Description

This sequence change creates a premature translational stop signal (p.Gln1017*) in the ATM gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual affected with breast cancer (PMID: 26681312). ClinVar contains an entry for this variant (Variation ID: 181992). Loss-of-function variants in ATM are known to be pathogenic (PMID: 23807571, 25614872). For these reasons, this variant has been classified as Pathogenic.

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

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000694246.2

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

Description

Variant summary: ATM c.3049C>T (p.Gln1017X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (e.g. c.3085dupA (p.Thr1029fsX19), c.3245_3247delinsTGAT (p.His1082fsX14), c.3372C>G (p.Tyr1124X)). The variant was absent in 251048 control chromosomes (gnomAD). c.3049C>T has been reported in the literature in an individual affected with Breast Cancer (Susswein_2016).To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three other clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014, and all laboratories classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.

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

Last Updated: Dec 4, 2021

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