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NM_000051.4(ATM):c.7456C>T (p.Arg2486Ter) AND Hereditary cancer-predisposing syndrome

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Aug 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:
RCV000115251.16

Allele description [Variation Report for NM_000051.4(ATM):c.7456C>T (p.Arg2486Ter)]

NM_000051.4(ATM):c.7456C>T (p.Arg2486Ter)

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.7456C>T (p.Arg2486Ter)
Other names:
p.R2486*:CGA>TGA; p.Arg2486Ter
HGVS:
  • NC_000011.10:g.108330362C>T
  • NG_009830.1:g.112531C>T
  • NG_054724.1:g.144471G>A
  • NM_000051.4:c.7456C>TMANE SELECT
  • NM_001330368.2:c.641-21291G>A
  • NM_001351110.2:c.*38+4858G>A
  • NM_001351834.2:c.7456C>T
  • NP_000042.3:p.Arg2486Ter
  • NP_000042.3:p.Arg2486Ter
  • NP_001338763.1:p.Arg2486Ter
  • LRG_135t1:c.7456C>T
  • LRG_135:g.112531C>T
  • LRG_135p1:p.Arg2486Ter
  • NC_000011.9:g.108201089C>T
  • NM_000051.3:c.7456C>T
  • p.Arg2486Stop
  • p.R2486*
Protein change:
R2486*
Links:
dbSNP: rs587779865
NCBI 1000 Genomes Browser:
rs587779865
Molecular consequence:
  • NM_001330368.2:c.641-21291G>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001351110.2:c.*38+4858G>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000051.4:c.7456C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001351834.2:c.7456C>T - nonsense - [Sequence Ontology: SO:0001587]

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

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000213694Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Pathogenic
(Aug 23, 2021) 		germlineclinical testing

PubMed (11)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

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

Citations

PubMed

Comprehensive scanning of the ATM gene with DOVAM-S.

Buzin CH, Gatti RA, Nguyen VQ, Wen CY, Mitui M, Sanal O, Chen JS, Nozari G, Mengos A, Li X, Fujimura F, Sommer SS.

Hum Mutat. 2003 Feb;21(2):123-31.

PubMed [citation]
PMID:
12552559

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
See all PubMed Citations (11)

Details of each submission

From Ambry Genetics, SCV000213694.7

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (11)

Description

The p.R2486* pathogenic mutation (also known as c.7456C>T), located in coding exon 49 of the ATM gene, results from a C to T substitution at nucleotide position 7456. This changes the amino acid from an arginine to a stop codon within coding exon 49. This mutation has been identified in multiple patients with ataxia-telangiectasia, either in a homozygous or compound heterozygous state (Buzin CH et al. Hum Mutat, 2003 Feb;21:123-31; Micol R et al. J Allergy Clin Immunol, 2011 Aug;128:382-9.e1; Méneret A et al. Neurology, 2014 Sep;83:1087-95; Berland A et al. J Allergy Clin Immunol, 2019 01;143:325-334.e2; Fiévet A et al. Hum Mutat, 2019 10;40:1713-1730). This mutation has also been reported in multiple patients with breast or pancreatic cancer (Susswein LR et al. Genet Med, 2016 08;18:823-32; Takai E et al. Oncotarget, 2016 Nov;7:74227-74235; Sun J et al. Clin Cancer Res, 2017 Oct;23:6113-6119; Ohmoto A et al. J Gastroenterol, 2018 Oct;53:1159-1167; Yang Z et al. Breast Cancer Res Treat, 2019 Apr;174:639-647). In addition to the information presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.

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

Last Updated: Nov 30, 2024