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NM_000051.4(ATM):c.6007-2A>G AND Ataxia-telangiectasia syndrome

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Oct 23, 2021
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV001976639.11

Allele description [Variation Report for NM_000051.4(ATM):c.6007-2A>G]

NM_000051.4(ATM):c.6007-2A>G

Genes:
ATM:ATM serine/threonine kinase [Gene - OMIM - HGNC]
C11orf65:chromosome 11 open reading frame 65 [Gene - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
11q22.3
Genomic location:
Preferred name:
NM_000051.4(ATM):c.6007-2A>G
HGVS:
  • NC_000011.10:g.108315821A>G
  • NG_009830.1:g.97990A>G
  • NG_054724.1:g.159012T>C
  • NM_000051.4:c.6007-2A>GMANE SELECT
  • NM_001330368.2:c.641-6750T>C
  • NM_001351110.2:c.*39-6750T>C
  • NM_001351834.2:c.6007-2A>G
  • LRG_135:g.97990A>G
  • NC_000011.9:g.108186548A>G
Links:
dbSNP: rs2136117225
NCBI 1000 Genomes Browser:
rs2136117225
Molecular consequence:
  • NM_001330368.2:c.641-6750T>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001351110.2:c.*39-6750T>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000051.4:c.6007-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001351834.2:c.6007-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]

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

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002267270Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Likely pathogenic
(Oct 23, 2021) 		germlineclinical testing

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

Help

Summary from all submissions

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

Citations

PubMed

Morphology and genomic hallmarks of breast tumours developed by ATM deleterious variant carriers.

Renault AL, Mebirouk N, Fuhrmann L, Bataillon G, Cavaciuti E, Le Gal D, Girard E, Popova T, La Rosa P, Beauvallet J, Eon-Marchais S, Dondon MG, d'Enghien CD, Laugé A, Chemlali W, Raynal V, Labbé M, Bièche I, Baulande S, Bay JO, Berthet P, Caron O, et al.

Breast Cancer Res. 2018 Apr 17;20(1):28. doi: 10.1186/s13058-018-0951-9.

PubMed [citation]
PMID:
29665859
PMCID:
PMC5905168

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
See all PubMed Citations (5)

Details of each submission

From Invitae, SCV002267270.3

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

Description

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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. Disruption of this splice site has been observed in individual(s) with breast cancer (PMID: 29665859). This variant is not present in population databases (ExAC no frequency). This sequence change affects an acceptor splice site in intron 40 of the ATM gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site 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).

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

Last Updated: May 1, 2024