NM_000251.3(MSH2):c.803C>A (p.Ser268Ter) AND Hereditary nonpolyposis colorectal neoplasms

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Mar 13, 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:: RCV002570409.3

Allele description [Variation Report for NM_000251.3(MSH2):c.803C>A (p.Ser268Ter)]

NM_000251.3(MSH2):c.803C>A (p.Ser268Ter)

Gene:

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

Variant type:

single nucleotide variant

Cytogenetic location:

2p21

Genomic location:

Preferred name:

NM_000251.3(MSH2):c.803C>A (p.Ser268Ter)

HGVS:

NC_000002.12:g.47414279C>A
NG_007110.2:g.16156C>A
NM_000251.3:c.803C>AMANE SELECT
NM_001258281.1:c.605C>A
NP_000242.1:p.Ser268Ter
NP_001245210.1:p.Ser202Ter
LRG_218:g.16156C>A
NC_000002.11:g.47641418C>A
NC_000002.11:g.47641418C>A
NM_000251.1:c.803C>A

Protein change:

S202*

Links:

dbSNP: rs563410947

NCBI 1000 Genomes Browser:

rs563410947

Molecular consequence:

NM_000251.3:c.803C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001258281.1:c.605C>A - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

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

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
SCV003524758	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Mar 13, 2022)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 27064304, 33191490, 15849733, 24362816, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003524758

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Mar 13, 2022)

germline

clinical testing

PubMed (5)
[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

Lynch syndrome mutation spectrum in New South Wales, Australia, including 55 novel mutations.

Sjursen W, McPhillips M, Scott RJ, Talseth-Palmer BA.

Mol Genet Genomic Med. 2016 Mar;4(2):223-31. doi: 10.1002/mgg3.198.

PubMed [citation]

PMID:: 27064304
PMCID:: PMC4799874

Spectrum of mutations in genes associated with familial colorectal cancer syndrome (MLH1, MSH2, PMS2, MSH6, and APC): A not so common hereditary cancer syndrome in Indian population.

Bhai P, Kulshrestha S, Puri RD, Bijarnia Mahay S, Saxena R, Verma IC.

Indian J Gastroenterol. 2020 Dec;39(6):599-607. doi: 10.1007/s12664-020-01096-x. Epub 2020 Nov 16.

PubMed [citation]

PMID:: 33191490

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003524758.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 973386). This premature translational stop signal has been observed in individual(s) with Lynch syndrome (PMID: 27064304, 33191490). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ser268*) 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