NM_000179.3(MSH6):c.2983G>T AND Hereditary cancer-predisposing syndrome

Clinical significance:Pathogenic (Last evaluated: Aug 26, 2016)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000491673.1

Allele description [Variation Report for NM_000179.3(MSH6):c.2983G>T]

NM_000179.3(MSH6):c.2983G>T

Gene:
MSH6:mutS homolog 6 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
2p16.3
Genomic location:
Preferred name:
NM_000179.3(MSH6):c.2983G>T
HGVS:
  • NC_000002.12:g.47800966G>T
  • NG_007111.1:g.22820G>T
  • NM_000179.2:c.2983G>T
  • NM_000179.3:c.2983G>TMANE SELECT
  • NM_001281492.1:c.2593G>T
  • NM_001281493.1:c.2077G>T
  • NM_001281494.1:c.2077G>T
  • NP_000170.1:p.Glu995Ter
  • NP_001268421.1:p.Glu865Ter
  • NP_001268422.1:p.Glu693Ter
  • NP_001268423.1:p.Glu693Ter
  • LRG_219t1:c.2983G>T
  • LRG_219:g.22820G>T
  • LRG_219p1:p.Glu995Ter
  • NC_000002.11:g.48028105G>T
Protein change:
E693*
Links:
dbSNP: rs63750258
NCBI 1000 Genomes Browser:
rs63750258
Molecular consequence:
  • NM_000179.2:c.2983G>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001281492.1:c.2593G>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001281493.1:c.2077G>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001281494.1:c.2077G>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

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000580375Ambry Geneticscriteria provided, single submitter
Pathogenic
(Aug 26, 2016)
germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown1not providednot provided1not providedclinical testing

Citations

PubMed

p53, CHK2, and CHK1 genes in Finnish families with Li-Fraumeni syndrome: further evidence of CHK2 in inherited cancer predisposition.

Vahteristo P, Tamminen A, Karvinen P, Eerola H, Eklund C, Aaltonen LA, Blomqvist C, Aittomäki K, Nevanlinna H.

Cancer Res. 2001 Aug 1;61(15):5718-22.

PubMed [citation]
PMID:
11479205

Molecular analysis of familial endometrial carcinoma: a manifestation of hereditary nonpolyposis colorectal cancer or a separate syndrome?

Ollikainen M, Abdel-Rahman WM, Moisio AL, Lindroos A, Kariola R, Järvelä I, Pöyhönen M, Butzow R, Peltomäki P.

J Clin Oncol. 2005 Jul 20;23(21):4609-16. Epub 2005 Apr 18.

PubMed [citation]
PMID:
15837969
See all PubMed Citations (3)

Details of each submission

From Ambry Genetics, SCV000580375.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (3)

Description

The p.E995* pathogenic mutation (also known as c.2983G>T), located in coding exon 4 of the MSH6 gene, results from a G to T substitution at nucleotide position 2983. This changes the amino acid from a glutamic acid to a stop codon within coding exon 4. This mutation has been reported in an individual diagnosed with both breast cancer and colorectal cancer at age 34 as well as in an individual diagnosed with a meningioma at age 51 from a family history meeting Amsterdam and/or revised Bethesda criteria for Lynch syndrome (Vahteristo P et al. Cancer Res., 2001 Aug;61:5718-22; Gylling AH et al. Carcinogenesis, 2008 Jul;29:1351-9). 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

Last Updated: Aug 27, 2021

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