NM_000051.4(ATM):c.5515C>T (p.Gln1839Ter) AND Ataxia-telangiectasia syndrome

Clinical significance:Pathogenic/Likely pathogenic (Last evaluated: Nov 15, 2017)

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:
RCV000169605.1

Allele description [Variation Report for NM_000051.4(ATM):c.5515C>T (p.Gln1839Ter)]

NM_000051.4(ATM):c.5515C>T (p.Gln1839Ter)

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.5515C>T (p.Gln1839Ter)
HGVS:
  • NC_000011.10:g.108304693C>T
  • NG_009830.1:g.86862C>T
  • NM_000051.4:c.5515C>TMANE SELECT
  • NM_001351834.2:c.5515C>T
  • NP_000042.3:p.Gln1839Ter
  • NP_000042.3:p.Gln1839Ter
  • NP_001338763.1:p.Gln1839Ter
  • LRG_135t1:c.5515C>T
  • LRG_135:g.86862C>T
  • LRG_135p1:p.Gln1839Ter
  • NC_000011.9:g.108175420C>T
  • NM_000051.3:c.5515C>T
Protein change:
Q1839*
Links:
dbSNP: rs786204751
NCBI 1000 Genomes Browser:
rs786204751
Molecular consequence:
  • NM_000051.4:c.5515C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001351834.2:c.5515C>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
SCV000221126Counsylcriteria provided, single submitter
Likely pathogenic
(Feb 13, 2015)
unknownliterature only

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

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

Citation Link,

SCV000748945Invitaecriteria provided, single submitter
Pathogenic
(Nov 15, 2017)
germlineclinical testing

PubMed (6)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedunknownunknownnot providednot providednot providednot providednot providedliterature only
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Cancer risks and mortality in heterozygous ATM mutation carriers.

Thompson D, Duedal S, Kirner J, McGuffog L, Last J, Reiman A, Byrd P, Taylor M, Easton DF.

J Natl Cancer Inst. 2005 Jun 1;97(11):813-22.

PubMed [citation]
PMID:
15928302

Classical ataxia telangiectasia patients have a congenitally aged immune system with high expression of CD95.

Carney EF, Srinivasan V, Moss PA, Taylor AM.

J Immunol. 2012 Jul 1;189(1):261-8. doi: 10.4049/jimmunol.1101909. Epub 2012 May 30.

PubMed [citation]
PMID:
22649200
See all PubMed Citations (6)

Details of each submission

From Counsyl, SCV000221126.1

#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, SCV000748945.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (6)

Description

This sequence change creates a premature translational stop signal (p.Gln1839*) 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 several individuals affected with ataxia telangiectasia (PMID: 9792409, 15928302, 22213089, 10873394, 22649200). ClinVar contains an entry for this variant (Variation ID: 189177). 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

Last Updated: Dec 4, 2021

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