NM_000051.4(ATM):c.4735C>T (p.Gln1579Ter) AND Ataxia-telangiectasia syndrome

Clinical significance:Pathogenic/Likely pathogenic (Last evaluated: Oct 3, 2020)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
4 submissions [Details]
Record status:
current
Accession:
RCV000234068.5

Allele description [Variation Report for NM_000051.4(ATM):c.4735C>T (p.Gln1579Ter)]

NM_000051.4(ATM):c.4735C>T (p.Gln1579Ter)

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.4735C>T (p.Gln1579Ter)
HGVS:
  • NC_000011.10:g.108293436C>T
  • NG_009830.1:g.75605C>T
  • NM_000051.3:c.4735C>T
  • NM_000051.4:c.4735C>TMANE SELECT
  • NM_001351834.2:c.4735C>T
  • NP_000042.3:p.Gln1579Ter
  • NP_000042.3:p.Gln1579Ter
  • NP_001338763.1:p.Gln1579Ter
  • LRG_135t1:c.4735C>T
  • LRG_135:g.75605C>T
  • LRG_135p1:p.Gln1579Ter
  • NC_000011.9:g.108164163C>T
Protein change:
Q1579*
Links:
dbSNP: rs869312755
NCBI 1000 Genomes Browser:
rs869312755
Molecular consequence:
  • NM_000051.3:c.4735C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_000051.4:c.4735C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001351834.2:c.4735C>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
SCV000282966Invitaecriteria provided, single submitter
Pathogenic
(Oct 3, 2020)
germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

SCV000678088Counsylcriteria provided, single submitter
Likely pathogenic
(Dec 14, 2016)
unknownclinical testing

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

Citation Link,

SCV000807210Baylor Geneticscriteria provided, single submitter
Pathogenic
(Sep 1, 2017)
maternalclinical testing

PubMed (2)
[See all records that cite these PMIDs]

SCV002018918PerkinElmer Genomicsno assertion criteria providedPathogenic
(Feb 25, 2019)
germlineclinical testing

Summary from all submissions

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

Citations

PubMed

Improving performance of multigene panels for genomic analysis of cancer predisposition.

Shirts BH, Casadei S, Jacobson AL, Lee MK, Gulsuner S, Bennett RL, Miller M, Hall SA, Hampel H, Hisama FM, Naylor LV, Goetsch C, Leppig K, Tait JF, Scroggins SM, Turner EH, Livingston R, Salipante SJ, King MC, Walsh T, Pritchard CC.

Genet Med. 2016 Oct;18(10):974-81. doi: 10.1038/gim.2015.212. Epub 2016 Feb 4.

PubMed [citation]
PMID:
26845104

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818
See all PubMed Citations (5)

Details of each submission

From Invitae, SCV000282966.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

This sequence change creates a premature translational stop signal at codon 1579 (p.Gln1579*) of the ATM gene. It is expected to result in an absent or disrupted protein product. Truncating variants in ATM are known to be pathogenic. This particular truncation has been reported in the literature in an individual affected with breast cancer (PMID: 26845104) and in an individual affected with ataxia telangiectasia (PMID: 25037873). For these reasons, this variant has been classified as Pathogenic.

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

From Counsyl, SCV000678088.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

From Baylor Genetics, SCV000807210.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing
(GTR000508680.4)
PubMed (2)

Description

This nonsense mutation is categorized as deleterious according to ACMG guidelines (PMID:18414213). It was found twice in our laboratory in trans with a deleterious frameshift mutation in a set of affected siblings. 9-year-old female & 12-year-old male sibs had cerebellar ataxia, oculomotor apraxia, intellectual disability, hypertonia, spasticity, peripheral neuropathy, pigmentary skin changes.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1maternalyesnot providednot providednot provided
(GTR000508680.4)
not providednot providednot providednot provided

From PerkinElmer Genomics, SCV002018918.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Nov 28, 2021

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