NM_000051.4(ATM):c.4019_4029del (p.Leu1340fs) AND Ataxia-telangiectasia syndrome

Clinical significance:Pathogenic/Likely pathogenic (Last evaluated: Jul 27, 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:
RCV000410743.4

Allele description [Variation Report for NM_000051.4(ATM):c.4019_4029del (p.Leu1340fs)]

NM_000051.4(ATM):c.4019_4029del (p.Leu1340fs)

Gene:
ATM:ATM serine/threonine kinase [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
11q22.3
Genomic location:
Preferred name:
NM_000051.4(ATM):c.4019_4029del (p.Leu1340fs)
HGVS:
  • NC_000011.10:g.108287625_108287635del
  • NG_009830.1:g.69794_69804del
  • NM_000051.3:c.4019_4029del
  • NM_000051.4:c.4019_4029delMANE SELECT
  • NM_001351834.2:c.4019_4029del
  • NP_000042.3:p.Leu1340fs
  • NP_000042.3:p.Leu1340fs
  • NP_001338763.1:p.Leu1340fs
  • LRG_135t1:c.4019_4029del
  • LRG_135:g.69794_69804del
  • LRG_135p1:p.Leu1340fs
  • NC_000011.9:g.108158349_108158359del
  • NC_000011.9:g.108158352_108158362del
  • NM_000051.3:c.4019_4029del
  • NM_000051.3:c.4019_4029delTACCAGAGATT
Protein change:
L1340fs
Links:
dbSNP: rs1057517140
NCBI 1000 Genomes Browser:
rs1057517140
Molecular consequence:
  • NM_000051.3:c.4019_4029del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_000051.4:c.4019_4029del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001351834.2:c.4019_4029del - 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
SCV000486809Counsylcriteria provided, single submitter
Likely pathogenic
(Aug 12, 2016)
unknownclinical testing

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

Citation Link,

SCV000547017Invitaecriteria provided, single submitter
Pathogenic
(Jul 27, 2020)
germlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing
not providedunknownunknownnot 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 (3)

Details of each submission

From Counsyl, SCV000486809.1

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

From Invitae, SCV000547017.5

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

Description

This sequence change creates a premature translational stop signal (p.Leu1340Cysfs*10) 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 not been reported in the literature in individuals with ATM-related disease. ClinVar contains an entry for this variant (Variation ID: 371269). 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: Nov 27, 2021

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