NM_000251.2(MSH2):c.2335dup (p.Met779fs) AND Lynch syndrome

Clinical significance:Pathogenic (Last evaluated: Sep 5, 2013)

Review status:3 stars out of maximum of 4 stars

reviewed by expert panel

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000076459.3

Allele description [Variation Report for NM_000251.2(MSH2):c.2335dup (p.Met779fs)]

NM_000251.2(MSH2):c.2335dup (p.Met779fs)

Gene:
MSH2:mutS homolog 2 [Gene - OMIM - HGNC]
Variant type:
Duplication
Cytogenetic location:
2p21
Genomic location:
Preferred name:
NM_000251.2(MSH2):c.2335dup (p.Met779fs)
HGVS:
  • NC_000002.12:g.47478396dup
  • NG_007110.2:g.80273dup
  • NM_000251.2:c.2335dup
  • NM_001258281.1:c.2137dup
  • NP_000242.1:p.Met779fs
  • NP_001245210.1:p.Met713fs
  • LRG_218t1:c.2335dup
  • LRG_218:g.80273dup
  • LRG_218p1:p.Met779fs
  • NC_000002.11:g.47705534_47705535insA
  • NC_000002.11:g.47705535dup
  • NM_000251.1:c.2335dup
  • NM_000251.1:c.2335dupA
  • NM_000251.2:c.2335dupA
Protein change:
M713fs
Links:
dbSNP: rs63750149
NCBI 1000 Genomes Browser:
rs63750149
Molecular consequence:
  • NM_000251.2:c.2335dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001258281.1:c.2137dup - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:
Lynch syndrome
Synonyms:
Familial nonpolyposis colon cancer
Identifiers:
MONDO: MONDO:0005835; MedGen: C4552100; OMIM: PS120435

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000107488International Society for Gastrointestinal Hereditary Tumours (InSiGHT)reviewed by expert panel
Pathogenic
(Sep 5, 2013)
germlineresearch

Citation Link,

SCV000917710Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
Likely pathogenic
(Apr 26, 2018)
germlineclinical testing

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

Citation Link

Description

SCV000107488

Summary from all submissions

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

Citations

PubMed

Reduction in hMSH2 mRNA levels by premature translation termination: implications for mutation screening in hereditary nonpolyposis colorectal cancer.

Lin X, Choi JH, Lynch P, Xi L, Wu E, Frazier ML.

Dig Dis Sci. 1999 Mar;44(3):553-9.

PubMed [citation]
PMID:
10080150

Details of each submission

From International Society for Gastrointestinal Hereditary Tumours (InSiGHT), SCV000107488.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedresearchnot provided

Description

Coding sequence variation introducing premature termination codon

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

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000917710.1

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

Description

Variant summary: MSH2 c.2335dupA (p.Met779AsnfsX8) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as likely pathogenic/pathogenic by our laboratory (eg. c.2460_2462delinsA (p.Val821fsX2), c.2466T>A (p.Cys822X), and c.2633_2634delAG (p.Glu878fsX3)). The variant was absent in 246228 control chromosomes (gnomAD). The variant, c.2335dupA, has been reported in the literature in an individual affected with Lynch Syndrome (Lin_1999). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. A ClinVar submission from a clinical diagnostic laboratory (evaluation after 2014) cites the variant as "pathogenic." Based on the evidence outlined above, the variant was classified as likely pathogenic.

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

Last Updated: Aug 27, 2021

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