NM_000251.3(MSH2):c.860dup (p.Gln288fs) AND Hereditary nonpolyposis colorectal neoplasms

Clinical significance:Pathogenic (Last evaluated: Jul 19, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001034633.2

Allele description [Variation Report for NM_000251.3(MSH2):c.860dup (p.Gln288fs)]

NM_000251.3(MSH2):c.860dup (p.Gln288fs)

Gene:
MSH2:mutS homolog 2 [Gene - OMIM - HGNC]
Variant type:
Duplication
Cytogenetic location:
2p21
Genomic location:
Preferred name:
NM_000251.3(MSH2):c.860dup (p.Gln288fs)
HGVS:
  • NC_000002.12:g.47414336dup
  • NG_007110.2:g.16213dup
  • NM_000251.2:c.860dup
  • NM_000251.3:c.860dupMANE SELECT
  • NM_001258281.1:c.662dup
  • NP_000242.1:p.Gln288fs
  • NP_000242.1:p.Gln288fs
  • NP_001245210.1:p.Gln222fs
  • LRG_218t1:c.860dup
  • LRG_218:g.16213dup
  • LRG_218p1:p.Gln288fs
  • NC_000002.11:g.47641473_47641474insG
  • NC_000002.11:g.47641475dup
  • NM_000251.1:c.860dupG
  • NM_000251.2:c.860dupG
  • p.Gln288ThrfsX3
  • p.Q288Tfs*3
Protein change:
Q222fs
Links:
dbSNP: rs193922375
NCBI 1000 Genomes Browser:
rs193922375
Molecular consequence:
  • NM_000251.2:c.860dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_000251.3:c.860dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001258281.1:c.662dup - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:
Hereditary nonpolyposis colorectal neoplasms
Identifiers:
MedGen: C0009405; Orphanet: 443090

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000284191Invitaecriteria provided, single submitter
Pathogenic
(Jul 19, 2020)
germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Summary from all submissions

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

Citations

PubMed

Mutation spectrum and risk of colorectal cancer in African American families with Lynch syndrome.

Guindalini RS, Win AK, Gulden C, Lindor NM, Newcomb PA, Haile RW, Raymond V, Stoffel E, Hall M, Llor X, Ukaegbu CI, Solomon I, Weitzel J, Kalady M, Blanco A, Terdiman J, Shuttlesworth GA, Lynch PM, Hampel H, Lynch HT, Jenkins MA, Olopade OI, et al.

Gastroenterology. 2015 Nov;149(6):1446-53. doi: 10.1053/j.gastro.2015.07.052. Epub 2015 Aug 3.

PubMed [citation]
PMID:
26248088
PMCID:
PMC4648287

Spectrum and frequencies of mutations in MSH2 and MLH1 identified in 1,721 German families suspected of hereditary nonpolyposis colorectal cancer.

Mangold E, Pagenstecher C, Friedl W, Mathiak M, Buettner R, Engel C, Loeffler M, Holinski-Feder E, Müller-Koch Y, Keller G, Schackert HK, Krüger S, Goecke T, Moeslein G, Kloor M, Gebert J, Kunstmann E, Schulmann K, Rüschoff J, Propping P.

Int J Cancer. 2005 Sep 20;116(5):692-702.

PubMed [citation]
PMID:
15849733
See all PubMed Citations (4)

Details of each submission

From Invitae, SCV000284191.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

This sequence change creates a premature translational stop signal (p.Gln288Thrfs*3) in the MSH2 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual affected with Lynch syndrome (PMID: 26248088). ClinVar contains an entry for this variant (Variation ID: 36579). Loss-of-function variants in MSH2 are known to be pathogenic (PMID: 15849733, 24362816). For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: Oct 25, 2021

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