NM_000051.4(ATM):c.1235+1G>A AND Ataxia-telangiectasia syndrome

Clinical significance:Likely pathogenic (Last evaluated: Mar 29, 2019)

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:
RCV000668841.5

Allele description [Variation Report for NM_000051.4(ATM):c.1235+1G>A]

NM_000051.4(ATM):c.1235+1G>A

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.1235+1G>A
HGVS:
  • NC_000011.10:g.108249103G>A
  • NG_009830.1:g.31272G>A
  • NM_000051.4:c.1235+1G>AMANE SELECT
  • NM_001351834.2:c.1235+1G>A
  • LRG_135t1:c.1235+1G>A
  • LRG_135:g.31272G>A
  • NC_000011.9:g.108119830G>A
  • NM_000051.3:c.1235+1G>A
Links:
dbSNP: rs1555069881
NCBI 1000 Genomes Browser:
rs1555069881
Molecular consequence:
  • NM_000051.4:c.1235+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001351834.2:c.1235+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]

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
SCV000793513Counsylcriteria provided, single submitter
Likely pathogenic
(Aug 18, 2017)
unknownclinical testing

Citation Link,

SCV000935847Invitaecriteria provided, single submitter
Likely pathogenic
(Mar 29, 2019)
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

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]
PMID:
16199547
PMCID:
PMC1735933

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, SCV000793513.1

#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, SCV000935847.3

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

Description

This sequence change affects a donor splice site in intron 9 of the ATM gene. It is expected to disrupt RNA splicing and likely results 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 conditions. ClinVar contains an entry for this variant (Variation ID: 553402). Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in ATM are known to be pathogenic (PMID: 23807571, 25614872). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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

Last Updated: Nov 27, 2021

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