NM_000251.3(MSH2):c.2041C>T (p.Gln681Ter) AND Lynch syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Aug 12, 2016
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000586396.1

Allele description [Variation Report for NM_000251.3(MSH2):c.2041C>T (p.Gln681Ter)]

NM_000251.3(MSH2):c.2041C>T (p.Gln681Ter)

Gene:

MSH2:mutS homolog 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2p21

Genomic location:

Preferred name:

NM_000251.3(MSH2):c.2041C>T (p.Gln681Ter)

HGVS:

NC_000002.12:g.47476402C>T
NG_007110.2:g.78279C>T
NM_000251.3:c.2041C>TMANE SELECT
NM_001258281.1:c.1843C>T
NP_000242.1:p.Gln681Ter
NP_000242.1:p.Gln681Ter
NP_001245210.1:p.Gln615Ter
LRG_218t1:c.2041C>T
LRG_218:g.78279C>T
LRG_218p1:p.Gln681Ter
NC_000002.11:g.47703541C>T
NM_000251.1:c.2041C>T
NM_000251.2:c.2041C>T

Protein change:

Q615*

Links:

dbSNP: rs730881762

NCBI 1000 Genomes Browser:

rs730881762

Molecular consequence:

NM_000251.3:c.2041C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001258281.1:c.1843C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Lynch syndrome
Identifiers:: MONDO: MONDO:0005835; MedGen: C4552100

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000696227	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Pathogenic (Aug 12, 2016)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 24710284, 12624141 LabCorp Variant Classification Summary - May 2015.docx Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000696227

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Pathogenic
(Aug 12, 2016)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

LabCorp Variant Classification Summary - May 2015.docx

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Systematic study on genetic and epimutational profile of a cohort of Amsterdam criteria-defined Lynch Syndrome in Singapore.

Liu Y, Chew MH, Goh XW, Tan SY, Loi CT, Tan YM, Law HY, Koh PK, Tang CL.

PLoS One. 2014;9(4):e94170. doi: 10.1371/journal.pone.0094170.

PubMed [citation]

PMID:: 24710284
PMCID:: PMC3978005

Cancer risk in 348 French MSH2 or MLH1 gene carriers.

Parc Y, Boisson C, Thomas G, Olschwang S.

J Med Genet. 2003 Mar;40(3):208-13. No abstract available.

PubMed [citation]

PMID:: 12624141
PMCID:: PMC1735402

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000696227.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

Variant summary: The MSH2 c.2041C>T (p.Gln681X) variant results in a premature termination codon, predicted to cause a truncated or absent MSH2 protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (e.g. c.2113delG, p.Val705fsX5; c.2152C>T, p.Gln718X; c.2633_2634delAG, p.Glu878fsX3). One in silico tool predicts a damaging outcome for this variant. The variant has been reported in affected individuals in the literature and is absent in 121330 control chromosomes. Taken together, this variant is classified as pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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