NM_000251.3(MSH2):c.680_683del (p.Arg227fs) AND Hereditary nonpolyposis colorectal neoplasms

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Apr 1, 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:: RCV001865531.6

Allele description [Variation Report for NM_000251.3(MSH2):c.680_683del (p.Arg227fs)]

NM_000251.3(MSH2):c.680_683del (p.Arg227fs)

Gene:

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

Variant type:

Microsatellite

Cytogenetic location:

2p21

Genomic location:

Preferred name:

NM_000251.3(MSH2):c.680_683del (p.Arg227fs)

HGVS:

NC_000002.12:g.47412444GAAA[1]
NG_007110.2:g.14321GAAA[1]
NM_000251.3:c.680_683delMANE SELECT
NM_001258281.1:c.482_485del
NP_000242.1:p.Arg227fs
NP_001245210.1:p.Arg161fs
LRG_218:g.14321GAAA[1]
NC_000002.11:g.47639582_47639585del
NC_000002.11:g.47639583GAAA[1]
NM_000251.1:c.680_683delGAAA
NM_000251.2:c.680_683delGAAA
p.R227Kfs*18

Protein change:

R161fs

Links:

dbSNP: rs587782537

NCBI 1000 Genomes Browser:

rs587782537

Molecular consequence:

NM_000251.3:c.680_683del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001258281.1:c.482_485del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

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

Recent activity

Clear Turn Off Turn On

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

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
SCV002238939	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Apr 1, 2022)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 18566915, 15849733, 24362816, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002238939

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Apr 1, 2022)

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

Major contribution from recurrent alterations and MSH6 mutations in the Danish Lynch syndrome population.

Nilbert M, Wikman FP, Hansen TV, Krarup HB, Orntoft TF, Nielsen FC, Sunde L, Gerdes AM, Cruger D, Timshel S, Bisgaard ML, Bernstein I, Okkels H.

Fam Cancer. 2009;8(1):75-83. doi: 10.1007/s10689-008-9199-3. Epub 2008 Jun 20.

PubMed [citation]

PMID:: 18566915

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, SCV002238939.3

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

Description

This variant is also known as c.675_678delAGAA (p.Lys228fs). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 428475). This premature translational stop signal has been observed in individual(s) with clinical features of Lynch syndrome (PMID: 18566915). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg227Lysfs*18) 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

ClinVar

Relating variation to medicine