NM_000051.4(ATM):c.802C>T (p.Gln268Ter) 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:
RCV000222842.2

Allele description [Variation Report for NM_000051.4(ATM):c.802C>T (p.Gln268Ter)]

NM_000051.4(ATM):c.802C>T (p.Gln268Ter)

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.802C>T (p.Gln268Ter)
HGVS:
  • NC_000011.10:g.108244927C>T
  • NG_009830.1:g.27096C>T
  • NM_000051.3:c.802C>T
  • NM_000051.4:c.802C>TMANE SELECT
  • NM_001351834.2:c.802C>T
  • NP_000042.3:p.Gln268Ter
  • NP_000042.3:p.Gln268Ter
  • NP_001338763.1:p.Gln268Ter
  • LRG_135t1:c.802C>T
  • LRG_135:g.27096C>T
  • LRG_135p1:p.Gln268Ter
  • NC_000011.9:g.108115654C>T
Protein change:
Q268*
Links:
dbSNP: rs557012154
NCBI 1000 Genomes Browser:
rs557012154
Molecular consequence:
  • NM_000051.3:c.802C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_000051.4:c.802C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001351834.2:c.802C>T - nonsense - [Sequence Ontology: SO:0001587]
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
SCV000278020Ambry Geneticscriteria provided, single submitter
Pathogenic
(Jul 6, 2018)
germlineclinical testing

Citation Link,

SCV001347034Color Health, Inccriteria provided, single submitter
Pathogenic
(Jan 15, 2020)
germlineclinical testing

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

Description

This variant changes 1 nucleotide in exon 7 of the ATM gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been identified in 1/251050 chromosomes 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.

SCV001347034

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown1not providednot provided1not 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 Ambry Genetics, SCV000278020.6

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testingnot provided

Description

The p.Q268* pathogenic mutation (also known as c.802C>T), located in coding exon 6 of the ATM gene, results from a C to T substitution at nucleotide position 802. This changes the amino acid from a glutamine to a stop codon within coding exon 6. This mutation has been previously identified in ataxia-telangiectasia patients (Teraoka SN et al. Am. J. Hum. Genet. 1999 Jun;64:1617-31; Buzin CH et al. Hum. Mutat. 2003 Feb;21:123-31. In addition to the clinical data 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
1germlineunknown1not providednot provided1not providednot providednot provided

From Color Health, Inc, SCV001347034.1

#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: Oct 30, 2021

Support Center