NM_000251.3(MSH2):c.686_687del (p.Lys229fs) AND Hereditary nonpolyposis colorectal neoplasms

Germline classification:: Pathogenic (1 submission)
Last evaluated:: May 1, 2023
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:: RCV000801666.5

Allele description [Variation Report for NM_000251.3(MSH2):c.686_687del (p.Lys229fs)]

NM_000251.3(MSH2):c.686_687del (p.Lys229fs)

Gene:

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

Variant type:

Deletion

Cytogenetic location:

2p21

Genomic location:

Preferred name:

NM_000251.3(MSH2):c.686_687del (p.Lys229fs)

HGVS:

NC_000002.12:g.47412454_47412455del
NG_007110.2:g.14331_14332del
NM_000251.3:c.686_687delMANE SELECT
NM_001258281.1:c.488_489del
NP_000242.1:p.Lys229fs
NP_001245210.1:p.Lys163fs
LRG_218:g.14331_14332del
NC_000002.11:g.47639588_47639589del
NC_000002.11:g.47639593_47639594del
NM_000251.1:c.686_687delAA
NM_000251.2:c.686_687delAA
p.K229SfsX2
p.Lys229SerfsX2

Protein change:

K163fs

Links:

dbSNP: rs63749897

NCBI 1000 Genomes Browser:

rs63749897

Molecular consequence:

NM_000251.3:c.686_687del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001258281.1:c.488_489del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Hereditary nonpolyposis colorectal neoplasms
Identifiers:: MeSH: D003123; MedGen: C0009405

Recent activity

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maltose alpha-D-glucosyltransferase [Xanthomonas citri pv. citri]
maltose alpha-D-glucosyltransferase [Xanthomonas citri pv. citri]
gi|2060257893|gnl|PRJNA727623|KJA71 0|gb|QXF02119.1|

Protein
treS [Xanthomonas hortorum]
treS [Xanthomonas hortorum]
Gene ID:55514165

Gene
treS [Rhizobium esperanzae]
treS [Rhizobium esperanzae]
Gene ID:58693144

Gene
treS [Mycolicibacterium fortuitum]
treS [Mycolicibacterium fortuitum]
Gene ID:29429045

Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000941454	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (May 1, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 26681312, 15849733, 24362816, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000941454

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(May 1, 2023)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

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

Pathogenic and likely pathogenic variant prevalence among the first 10,000 patients referred for next-generation cancer panel testing.

Susswein LR, Marshall ML, Nusbaum R, Vogel Postula KJ, Weissman SM, Yackowski L, Vaccari EM, Bissonnette J, Booker JK, Cremona ML, Gibellini F, Murphy PD, Pineda-Alvarez DE, Pollevick GD, Xu Z, Richard G, Bale S, Klein RT, Hruska KS, Chung WK.

Genet Med. 2016 Aug;18(8):823-32. doi: 10.1038/gim.2015.166. Epub 2015 Dec 17. Erratum in: Genet Med. 2016 May;18(5):531-2. doi: 10.1038/gim.2016.21.

PubMed [citation]

PMID:: 26681312
PMCID:: PMC4985612

Spectrum and frequencies of mutations in MSH2 and MLH1 identified in 1,721 German families suspected of hereditary nonpolyposis colorectal cancer.

Mangold E, Pagenstecher C, Friedl W, Mathiak M, Buettner R, Engel C, Loeffler M, Holinski-Feder E, Müller-Koch Y, Keller G, Schackert HK, Krüger S, Goecke T, Moeslein G, Kloor M, Gebert J, Kunstmann E, Schulmann K, Rüschoff J, Propping P.

Int J Cancer. 2005 Sep 20;116(5):692-702.

PubMed [citation]

PMID:: 15849733

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000941454.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 127650). This premature translational stop signal has been observed in individual(s) with colon cancer (PMID: 26681312). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Lys229Serfs*2) in the MSH2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MSH2 are known to be pathogenic (PMID: 15849733, 24362816).

#	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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