NM_000251.3(MSH2):c.34dup (p.Glu12fs) AND Hereditary nonpolyposis colon cancer

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Sep 27, 2022
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:: RCV002298463.1

Allele description [Variation Report for NM_000251.3(MSH2):c.34dup (p.Glu12fs)]

NM_000251.3(MSH2):c.34dup (p.Glu12fs)

Gene:

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

Variant type:

Duplication

Cytogenetic location:

2p21

Genomic location:

Preferred name:

NM_000251.3(MSH2):c.34dup (p.Glu12fs)

HGVS:

NC_000002.12:g.47403225dup
NG_007110.2:g.5102dup
NM_000251.3:c.34dupMANE SELECT
NM_001258281.1:c.-31+50dup
NP_000242.1:p.Glu12fs
NP_000242.1:p.Glu12fs
LRG_218t1:c.34dup
LRG_218:g.5102dup
LRG_218p1:p.Glu12fs
NC_000002.11:g.47630362_47630363insG
NC_000002.11:g.47630364dup
NM_000251.1:c.34dup
NM_000251.1:c.34dupG
NM_000251.2:c.34dup
NM_000251.2:c.34dupG

Protein change:

E12fs

Links:

dbSNP: rs63750614

NCBI 1000 Genomes Browser:

rs63750614

Molecular consequence:

NM_000251.3:c.34dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001258281.1:c.-31+50dup - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Name:: Hereditary nonpolyposis colon cancer (HNPCC)
Synonyms:: Hereditary nonpolyposis colorectal cancer; Familial nonpolyposis colon cancer; Hereditary Nonpolyposis Colorectal Cancer Syndrome
Identifiers:: MONDO: MONDO:0018630; MedGen: C1333990; OMIM: PS120435

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002598590	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Pathogenic (Sep 27, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 31844177, 14504054 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002598590

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

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Pathogenic
(Sep 27, 2022)

germline

clinical testing

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

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

Prevalence of pathogenic germline cancer risk variants in high-risk urothelial carcinoma.

Nassar AH, Abou Alaiwi S, AlDubayan SH, Moore N, Mouw KW, Kwiatkowski DJ, Choueiri TK, Curran C, Berchuck JE, Harshman LC, Nuzzo PV, Chanza NM, Van Allen E, Esplin ED, Yang S, Callis T, Garber JE, Rana HQ, Sonpavde G.

Genet Med. 2020 Apr;22(4):709-718. doi: 10.1038/s41436-019-0720-x. Epub 2019 Dec 17.

PubMed [citation]

PMID:: 31844177
PMCID:: PMC7118025

Microsatellite instability and mutation analysis among southern Italian patients with colorectal carcinoma: detection of different alterations accounting for MLH1 and MSH2 inactivation in familial cases.

Colombino M, Cossu A, Arba A, Manca A, Curci A, Avallone A, Comella G, Botti G, Scintu F, Amoruso M, D'Abbicco D, d'Agnessa MR, Spanu A, Tanda F, Palmieri G.

Ann Oncol. 2003 Oct;14(10):1530-6.

PubMed [citation]

PMID:: 14504054

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV002598590.1

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

Description

Variant summary: MSH2 c.34dupG (p.Glu12GlyfsX70) 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 pathogenic by our laboratory. The variant was absent in 223170 control chromosomes. c.34dupG has been reported in the literature in individuals affected with Lynch Syndrome. These data indicate that the variant is likely to be associated with disease. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic. Based on the evidence outlined above, the variant was 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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