NM_000051.4(ATM):c.3880dup (p.Ile1294fs) AND Ataxia-telangiectasia syndrome

Clinical significance:Pathogenic/Likely pathogenic (Last evaluated: Jul 30, 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:
RCV000410605.4

Allele description [Variation Report for NM_000051.4(ATM):c.3880dup (p.Ile1294fs)]

NM_000051.4(ATM):c.3880dup (p.Ile1294fs)

Gene:
ATM:ATM serine/threonine kinase [Gene - OMIM - HGNC]
Variant type:
Duplication
Cytogenetic location:
11q22.3
Genomic location:
Preferred name:
NM_000051.4(ATM):c.3880dup (p.Ile1294fs)
HGVS:
  • NC_000011.10:g.108284360dup
  • NG_009830.1:g.66529dup
  • NM_000051.4:c.3880dupMANE SELECT
  • NM_001351834.2:c.3880dup
  • NP_000042.3:p.Ile1294fs
  • NP_000042.3:p.Ile1294fs
  • NP_001338763.1:p.Ile1294fs
  • LRG_135t1:c.3880dup
  • LRG_135:g.66529dup
  • LRG_135p1:p.Ile1294fs
  • NC_000011.9:g.108155086_108155087insA
  • NC_000011.9:g.108155087dup
  • NM_000051.3:c.3880dup
  • NM_000051.3:c.3880dupA
Protein change:
I1294fs
Links:
dbSNP: rs1057516541
NCBI 1000 Genomes Browser:
rs1057516541
Molecular consequence:
  • NM_000051.4:c.3880dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001351834.2:c.3880dup - frameshift variant - [Sequence Ontology: SO:0001589]

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
SCV000485847Counsylcriteria provided, single submitter
Likely pathogenic
(Feb 23, 2016)
unknownclinical testing

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

mdi-5618_320494_Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015).pdf,

Citation Link,

SCV000937930Invitaecriteria provided, single submitter
Pathogenic
(Jul 30, 2020)
germlineclinical testing

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

Summary from all submissions

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

Citations

PubMed

Functional characterization connects individual patient mutations in ataxia telangiectasia mutated (ATM) with dysfunction of specific DNA double-strand break-repair signaling pathways.

Keimling M, Volcic M, Csernok A, Wieland B, Dörk T, Wiesmüller L.

FASEB J. 2011 Nov;25(11):3849-60. doi: 10.1096/fj.11-185546. Epub 2011 Jul 21.

PubMed [citation]
PMID:
21778326

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
See all PubMed Citations (4)

Details of each submission

From Counsyl, SCV000485847.1

#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 Invitae, SCV000937930.3

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

Description

This sequence change creates a premature translational stop signal (p.Ile1294Asnfs*8) 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 observed in combination with another ATM variant in an individual affected with ataxia telangiectasia (PMID: 21778326). This variant is also known as c.3880fs in the literature. ClinVar contains an entry for this variant (Variation ID: 370505). 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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