NM_000251.3(MSH2):c.860dup (p.Gln288fs) AND Hereditary cancer-predisposing syndrome

Clinical significance:Pathogenic (Last evaluated: Jul 21, 2017)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000162420.3

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]
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
SCV000212761Ambry Geneticscriteria provided, single submitter
Pathogenic
(Jul 21, 2017)
germlineclinical testing

PubMed (2)
[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

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

Multigene Panel Testing Provides a New Perspective on Lynch Syndrome.

Espenschied CR, LaDuca H, Li S, McFarland R, Gau CL, Hampel H.

J Clin Oncol. 2017 Aug 1;35(22):2568-2575. doi: 10.1200/JCO.2016.71.9260. Epub 2017 May 17.

PubMed [citation]
PMID:
28514183
PMCID:
PMC7186580

Details of each submission

From Ambry Genetics, SCV000212761.6

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

Description

The c.860dupG pathogenic mutation, located in coding exon 5 of the MSH2 gene, results from a duplication of G at nucleotide position 860, causing a translational frameshift with a predicted alternate stop codon (p.Q288Tfs*3). This pathogenic mutation has been reported in multiple individuals with a personal and/or family history of cancers associated with Lynch syndrome (Guindalini RS et al. Gastroenterology. 2015 Nov;149:1446-53; Espenschied CR et al. J. Clin. Oncol. 2017 Aug;35(22):2568-2575). 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: Nov 27, 2021

Support Center