NM_000051.4(ATM):c.2921+1G>C AND Ataxia-telangiectasia syndrome

Clinical significance:Pathogenic/Likely pathogenic (Last evaluated: Jul 14, 2020)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
3 submissions [Details]
Record status:
current
Accession:
RCV000167947.7

Allele description [Variation Report for NM_000051.4(ATM):c.2921+1G>C]

NM_000051.4(ATM):c.2921+1G>C

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.2921+1G>C
HGVS:
  • NC_000011.10:g.108271147G>C
  • NG_009830.1:g.53316G>C
  • NM_000051.4:c.2921+1G>CMANE SELECT
  • NM_001351834.2:c.2921+1G>C
  • LRG_135t1:c.2921+1G>C
  • LRG_135:g.53316G>C
  • NC_000011.9:g.108141874G>C
  • NM_000051.3:c.2921+1G>C
Links:
dbSNP: rs587781558
NCBI 1000 Genomes Browser:
rs587781558
Molecular consequence:
  • NM_000051.4:c.2921+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001351834.2:c.2921+1G>C - 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
SCV000218595Invitaecriteria provided, single submitter
Pathogenic
(Jul 14, 2020)
germlineclinical testing

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

SCV000795509Counsylcriteria provided, single submitter
Likely pathogenic
(Nov 8, 2017)
unknownclinical testing

Citation Link,

SCV002021918PerkinElmer Genomicsno assertion criteria providedPathogenic
(Feb 1, 2019)
germlineclinical testing

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

Novel mutations and defective protein kinase C activation of T-lymphocytes in ataxia telangiectasia.

García-Pérez MA, Allende LM, Corell A, Varela P, Moreno AA, Sotoca A, Moreno A, Paz-Artal E, Barreiro E, Arnaiz-Villena A.

Clin Exp Immunol. 2001 Mar;123(3):472-80.

PubMed [citation]
PMID:
11298136
PMCID:
PMC1906002

Independent mutational events are rare in the ATM gene: haplotype prescreening enhances mutation detection rate.

Mitui M, Campbell C, Coutinho G, Sun X, Lai CH, Thorstenson Y, Castellvi-Bel S, Fernandez L, Monros E, Carvalho BT, Porras O, Fontan G, Gatti RA.

Hum Mutat. 2003 Jul;22(1):43-50.

PubMed [citation]
PMID:
12815592
See all PubMed Citations (5)

Details of each submission

From Invitae, SCV000218595.7

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

This sequence change affects a donor splice site in intron 19 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) and has not been reported in the literature in individuals with an ATM-related disease. ClinVar contains an entry for this variant (Variation ID: 188097). A different nucleotide change at this position, c.2921+1G>A, has been reported in individuals affected with ataxia-telangiectasia both in the homozygous state and as compound heterozygous with a second pathogenic ATM variant (PMID: 8845835, 11298136, 12815592, 23322442). The G>A sequence change has been reported to lead to aberrant splicing and exon skipping (PMID: 8845835). These data indicate that this nucleotide is crucial for normal RNA splicing. 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, SCV000795509.1

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

From PerkinElmer Genomics, SCV002021918.1

#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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