NM_000251.3(MSH2):c.2297del (p.Ile766fs) AND Hereditary nonpolyposis colon cancer

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 25, 2021
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:: RCV001778790.1

Allele description [Variation Report for NM_000251.3(MSH2):c.2297del (p.Ile766fs)]

NM_000251.3(MSH2):c.2297del (p.Ile766fs)

Gene:

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

Variant type:

Deletion

Cytogenetic location:

2p21

Genomic location:

Preferred name:

NM_000251.3(MSH2):c.2297del (p.Ile766fs)

HGVS:

NC_000002.12:g.47478358del
NG_007110.2:g.80235del
NM_000251.3:c.2297delMANE SELECT
NM_001258281.1:c.2099del
NP_000242.1:p.Ile766fs
NP_001245210.1:p.Ile700fs
LRG_218:g.80235del
NC_000002.11:g.47705497del
NM_000251.1:c.2297delT
NM_000251.2:c.2297delT

Protein change:

I700fs

Links:

dbSNP: rs863225394

NCBI 1000 Genomes Browser:

rs863225394

Molecular consequence:

NM_000251.3:c.2297del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001258281.1:c.2099del - frameshift variant - [Sequence Ontology: SO:0001589]

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
SCV002015055	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Pathogenic (Oct 25, 2021)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 21056691, 28944238 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002015055

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

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Pathogenic
(Oct 25, 2021)

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 alterations in DNA mismatch repair genes in patients with young-onset colorectal cancer.

Limburg PJ, Harmsen WS, Chen HH, Gallinger S, Haile RW, Baron JA, Casey G, Woods MO, Thibodeau SN, Lindor NM.

Clin Gastroenterol Hepatol. 2011 Jun;9(6):497-502. doi: 10.1016/j.cgh.2010.10.021. Epub 2010 Nov 5.

PubMed [citation]

PMID:: 21056691
PMCID:: PMC3058119

Targeted sequencing of 36 known or putative colorectal cancer susceptibility genes.

DeRycke MS, Gunawardena S, Balcom JR, Pickart AM, Waltman LA, French AJ, McDonnell S, Riska SM, Fogarty ZC, Larson MC, Middha S, Eckloff BW, Asmann YW, Ferber MJ, Haile RW, Gallinger S, Clendenning M, Rosty C, Win AK, Buchanan DD, Hopper JL, Newcomb PA, et al.

Mol Genet Genomic Med. 2017 Sep;5(5):553-569. doi: 10.1002/mgg3.317.

PubMed [citation]

PMID:: 28944238
PMCID:: PMC5606870

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV002015055.1

#	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.2297delT (p.Ile766AsnfsX46) 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. The variant was absent in 251442 control chromosomes (gnomAD). c.2297delT has been reported in the literature in at-least one individual affected with Lynch Syndrome who has been subsequently cited by others (example, Limburg_2011, DeRycke_2017). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar and 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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