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NM_000051.4(ATM):c.3747-1G>T AND Hereditary cancer-predisposing syndrome

Germline classification:
Pathogenic (1 submission)
Last evaluated:
May 13, 2022
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:
RCV002349264.2

Allele description [Variation Report for NM_000051.4(ATM):c.3747-1G>T]

NM_000051.4(ATM):c.3747-1G>T

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.3747-1G>T
HGVS:
  • NC_000011.10:g.108284226G>T
  • NG_009830.1:g.66395G>T
  • NM_000051.4:c.3747-1G>TMANE SELECT
  • NM_001351834.2:c.3747-1G>T
  • LRG_135t1:c.3747-1G>T
  • LRG_135:g.66395G>T
  • NC_000011.9:g.108154953G>T
  • NM_000051.3:c.3747-1G>T
Molecular consequence:
  • NM_000051.4:c.3747-1G>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001351834.2:c.3747-1G>T - 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
SCV002621244Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Pathogenic
(May 13, 2022) 		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

Morbidity and mortality from ataxia-telangiectasia are associated with ATM genotype.

Micol R, Ben Slama L, Suarez F, Le Mignot L, Beauté J, Mahlaoui N, Dubois d'Enghien C, Laugé A, Hall J, Couturier J, Vallée L, Delobel B, Rivier F, Nguyen K, Billette de Villemeur T, Stephan JL, Bordigoni P, Bertrand Y, Aladjidi N, Pedespan JM, Thomas C, Pellier I, et al.

J Allergy Clin Immunol. 2011 Aug;128(2):382-9.e1. doi: 10.1016/j.jaci.2011.03.052. Epub 2011 Jun 12.

PubMed [citation]
PMID:
21665257

Details of each submission

From Ambry Genetics, SCV002621244.2

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

Description

The c.3747-1G>T intronic pathogenic mutation results from a G to T substitution one nucleotide upstream from coding exon 25 of the ATM gene. This variant has been identified likely in trans with an ATM pathogenic variant in an individual diagnosed with ataxia-telangiectasia (Micol R et al. J Allergy Clin Immunol, 2011 Aug;128:382-9.e1). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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). In addition to the clinical data presented in the literature, 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 8, 2024