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NM_000051.4(ATM):c.1899-2A>C AND Hereditary cancer-predisposing syndrome

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jun 12, 2023
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:
RCV003289514.4

Allele description [Variation Report for NM_000051.4(ATM):c.1899-2A>C]

NM_000051.4(ATM):c.1899-2A>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.1899-2A>C
HGVS:
  • NC_000011.10:g.108253812A>C
  • NG_009830.1:g.35981A>C
  • NM_000051.3:c.1899-2A>C
  • NM_000051.4:c.1899-2A>CMANE SELECT
  • NM_001351834.2:c.1899-2A>C
  • LRG_135t1:c.1899-2A>C
  • LRG_135:g.35981A>C
  • NC_000011.9:g.108124539A>C
Molecular consequence:
  • NM_000051.4:c.1899-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001351834.2:c.1899-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]

Condition(s)

Name:
Hereditary cancer-predisposing syndrome
Synonyms:
Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

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Assertion and evidence details

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Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004009305Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Pathogenic
(Jun 12, 2023) 		germlineclinical testing

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

Citation Link

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Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot 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

Details of each submission

From Ambry Genetics, SCV004009305.3

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

Description

The c.1899-2A>C intronic pathogenic mutation results from an A to C substitution two nucleotides upstream from coding exon 12 in the ATM gene. This alteration, described as IVS15-2A>C, was reported in conjunction with another pathogenic alteration in ATM (IVS21+1G>CA) in a patient with a clinical diagnosis of ataxia telangiectasia (García-Pérez MA et al. Clin Exp Immunol. 2001 Mar;123:472-80). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice acceptor site and will result in the creation or strengthening of a novel splice acceptor site; however, direct evidence is insufficient at this time (Ambry internal data). Alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. As such, this alteration is classified as a disease-causing mutation.

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

Last Updated: Sep 29, 2024