NM_000051.4(ATM):c.3381_3384del (p.Gln1128fs) AND Hereditary cancer-predisposing syndrome

Clinical significance:Pathogenic (Last evaluated: Jan 15, 2020)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000130359.5

Allele description [Variation Report for NM_000051.4(ATM):c.3381_3384del (p.Gln1128fs)]

NM_000051.4(ATM):c.3381_3384del (p.Gln1128fs)

Gene:
ATM:ATM serine/threonine kinase [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
11q22.3
Genomic location:
Preferred name:
NM_000051.4(ATM):c.3381_3384del (p.Gln1128fs)
HGVS:
  • NC_000011.10:g.108279587_108279590del
  • NG_009830.1:g.61756_61759del
  • NM_000051.4:c.3381_3384delMANE SELECT
  • NM_001351834.2:c.3381_3384del
  • NP_000042.3:p.Gln1128fs
  • NP_000042.3:p.Gln1128fs
  • NP_001338763.1:p.Gln1128fs
  • LRG_135t1:c.3381_3384del
  • LRG_135:g.61756_61759del
  • LRG_135p1:p.Gln1128fs
  • NC_000011.9:g.108150314_108150317del
  • NM_000051.3:c.3381_3384del
  • NM_000051.3:c.3381_3384delTCAG
  • p.Q1128Kfs*3
Protein change:
Q1128fs
Links:
dbSNP: rs587781971
NCBI 1000 Genomes Browser:
rs587781971
Molecular consequence:
  • NM_000051.4:c.3381_3384del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001351834.2:c.3381_3384del - frameshift variant - [Sequence Ontology: SO:0001589]
Observations:
1

Condition(s)

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

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000185210Ambry Geneticscriteria provided, single submitter
Pathogenic
(Oct 16, 2017)
germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link,

SCV000911666Color Health, Inccriteria provided, single submitter
Pathogenic
(Jan 15, 2020)
germlineclinical testing

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

Description

This variant deletes 4 nucleotides in exon 23 of the ATM gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of ATM function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.

SCV000911666

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown1not providednot provided1not providedclinical testing

Citations

PubMed

New mutations, polymorphisms, and rare variants in the ATM gene detected by a novel SSCP strategy.

CastellvĂ­-Bel S, Sheikhavandi S, Telatar M, Tai LQ, Hwang M, Wang Z, Yang Z, Cheng R, Gatti RA.

Hum Mutat. 1999;14(2):156-62.

PubMed [citation]
PMID:
10425038

Frequency of Germline Mutations in 25 Cancer Susceptibility Genes in a Sequential Series of Patients With Breast Cancer.

Tung N, Lin NU, Kidd J, Allen BA, Singh N, Wenstrup RJ, Hartman AR, Winer EP, Garber JE.

J Clin Oncol. 2016 May 1;34(13):1460-8. doi: 10.1200/JCO.2015.65.0747. Epub 2016 Mar 14.

PubMed [citation]
PMID:
26976419
PMCID:
PMC4872307
See all PubMed Citations (3)

Details of each submission

From Ambry Genetics, SCV000185210.6

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (2)

Description

The c.3381_3384delTCAG pathogenic mutation, located in coding exon 22 of the ATM gene, results from a deletion of 4 nucleotides at nucleotide positions 3381 to 3384, causing a translational frameshift with a predicted alternate stop codon. This pathogenic mutation (designated as 3381delTCAG) was reported in an individual with ataxia-telangiectasia, although it was not noted whether a second mutation was identified (Castellví-Bel S et al. Hum. Mutat. 1999; 14(2):156-62). This mutation was also observed in conjunction with a BRCA2 pathogenic mutation in an individual diagnosed with breast cancer at age 33 who had a family history of breast, pancreatic, thyroid and esophageal cancer (Tung N et al. J. Clin. Oncol. 2016 May; 34(13):1460-8). 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
1germlineunknown1not providednot provided1not providednot providednot provided

From Color Health, Inc, SCV000911666.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Dec 4, 2021

Support Center