NM_000051.4(ATM):c.7913G>A (p.Trp2638Ter) AND multiple conditions

Clinical significance:Pathogenic (Last evaluated: Jan 18, 2018)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000768151.1

Allele description [Variation Report for NM_000051.4(ATM):c.7913G>A (p.Trp2638Ter)]

NM_000051.4(ATM):c.7913G>A (p.Trp2638Ter)

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.7913G>A (p.Trp2638Ter)
Other names:
p.W2638*:TGG>TAG
HGVS:
  • NC_000011.10:g.108332886G>A
  • NG_009830.1:g.115055G>A
  • NG_054724.1:g.141947C>T
  • NM_000051.4:c.7913G>AMANE SELECT
  • NM_001330368.2:c.641-23815C>T
  • NM_001351110.2:c.*38+2334C>T
  • NM_001351834.2:c.7913G>A
  • NP_000042.3:p.Trp2638Ter
  • NP_001338763.1:p.Trp2638Ter
  • LRG_135t1:c.7913G>A
  • LRG_135:g.115055G>A
  • NC_000011.9:g.108203613G>A
  • NC_000011.9:g.108203613G>A
  • NM_000051.3:c.7913G>A
  • p.W2638*
Protein change:
W2638*
Links:
dbSNP: rs377349459
NCBI 1000 Genomes Browser:
rs377349459
Molecular consequence:
  • NM_001330368.2:c.641-23815C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001351110.2:c.*38+2334C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000051.4:c.7913G>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001351834.2:c.7913G>A - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:
Familial cancer of breast
Synonyms:
Breast cancer, familial; CHEK2-Related Breast Cancer
Identifiers:
MONDO: MONDO:0016419; MedGen: C0346153; OMIM: 114480
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
SCV000898530Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicagocriteria provided, single submitter
Pathogenic
(Jan 18, 2018)
germlineclinical testing

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

Summary from all submissions

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

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago, SCV000898530.1

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

Description

ATM NM_000051.3 exon 53 p.Trp2638* (c.7913G>A): This variant has been identified as homozygous or compound heterozygous in at least 6 individuals with ataxia telangiectasia (Sasaki 1998 PMID:9711876, Mitui 2003 PMID:12815592, Coutinho 2004 PMID:15039971, Demuth 2011 PMID:21965147). This variant was also identified in at least 2 individuals with colon or prostate cancer (Pritchard 2016 PMID:27433846, Susswein 2016 PMID:26681312). This variant is present in 4/24010 African alleles in the Genome Aggregation Database (http://gnomad.broadinstitute.org/rs377349459). Please note, disease causing variants may be present in control databases at low frequencies, reflective of the general population and/or variable expressivity. This variant is present in ClinVar, with several labs classifying this variant as pathogenic or likely pathogenic (Variation ID:141233). Evolutionary conservation and computational predictive tools for this variant are limited or unavailable. This variant creates a premature stop at this codon which results in an absent or abnormal protein. Loss of function variants are a known mechanism of disease for this gene (Huang 2013 PMID:23807571) . In summary, this variant is classified as pathogenic.

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

Last Updated: Nov 27, 2021

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