NM_000251.3(MSH2):c.703_709del (p.Lys235fs) AND Hereditary nonpolyposis colon cancer

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Apr 12, 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:: RCV001375582.1

Allele description [Variation Report for NM_000251.3(MSH2):c.703_709del (p.Lys235fs)]

NM_000251.3(MSH2):c.703_709del (p.Lys235fs)

Gene:

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

Variant type:

Deletion

Cytogenetic location:

2p21

Genomic location:

Preferred name:

NM_000251.3(MSH2):c.703_709del (p.Lys235fs)

HGVS:

NC_000002.12:g.47412471_47412477del
NG_007110.2:g.14348_14354del
NM_000251.3:c.703_709delMANE SELECT
NM_001258281.1:c.505_511del
NP_000242.1:p.Lys235fs
NP_001245210.1:p.Lys169fs
LRG_218t1:c.703_709del
LRG_218:g.14348_14354del
NC_000002.11:g.47639610_47639616del
NM_000251.2:c.703_709delAAAGACA

Protein change:

K169fs

Links:

dbSNP: rs2104102733

NCBI 1000 Genomes Browser:

rs2104102733

Molecular consequence:

NM_000251.3:c.703_709del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001258281.1:c.505_511del - 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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001572478	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Likely pathogenic (Apr 12, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001572478

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

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Likely pathogenic
(Apr 12, 2021)

germline

clinical testing

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

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

Role of Tumor Mutation Burden Analysis in Detecting Lynch Syndrome in Precision Medicine: Analysis of 2,501 Japanese Cancer Patients.

Kiyozumi Y, Matsubayashi H, Higashigawa S, Horiuchi Y, Kado N, Hirashima Y, Shiomi A, Oishi T, Ohnami S, Ohshima K, Urakami K, Nagashima T, Yamaguchi K.

Cancer Epidemiol Biomarkers Prev. 2021 Jan;30(1):166-174. doi: 10.1158/1055-9965.EPI-20-0694. Epub 2020 Oct 12.

PubMed [citation]

PMID:: 33046448

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001572478.1

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

Description

Variant summary: MSH2 c.703_709delAAAGACA (p.Lys235PhefsX9) 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 251364 control chromosomes (gnomAD). c.703_709delAAAGACA has been reported in the literature in one individual affected with endometrial cancer (Kiyozumi_2020). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely 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: Dec 30, 2023

ClinVar

Relating variation to medicine