NM_000251.3(MSH2):c.842C>G (p.Ser281Ter) AND Hereditary cancer-predisposing syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: May 5, 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:: RCV000491522.4

Allele description [Variation Report for NM_000251.3(MSH2):c.842C>G (p.Ser281Ter)]

NM_000251.3(MSH2):c.842C>G (p.Ser281Ter)

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.842C>G (p.Ser281Ter)

HGVS:

NC_000002.12:g.47414318C>G
NG_007110.2:g.16195C>G
NM_000251.3:c.842C>GMANE SELECT
NM_001258281.1:c.644C>G
NP_000242.1:p.Ser281Ter
NP_000242.1:p.Ser281Ter
NP_001245210.1:p.Ser215Ter
LRG_218t1:c.842C>G
LRG_218:g.16195C>G
LRG_218p1:p.Ser281Ter
NC_000002.11:g.47641457C>G
NM_000251.1:c.842C>G
NM_000251.2:c.842C>G

Protein change:

S215*

Links:

dbSNP: rs63749991

NCBI 1000 Genomes Browser:

rs63749991

Molecular consequence:

NM_000251.3:c.842C>G - nonsense - [Sequence Ontology: SO:0001587]
NM_001258281.1:c.644C>G - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Hereditary cancer-predisposing syndrome
Synonyms:: Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000580389	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (May 5, 2021)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 17653898, 21311894, 25186627, 28944238, 30918532 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000580389

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(May 5, 2021)

germline

clinical testing

PubMed (5)
[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

Nine novel pathogenic germline mutations in MLH1, MSH2, MSH6 and PMS2 in families with Lynch syndrome.

Rahner N, Friedrichs N, Wehner M, Steinke V, Aretz S, Friedl W, Buettner R, Mangold E, Propping P, Walldorf C.

Acta Oncol. 2007;46(6):763-9.

PubMed [citation]

PMID:: 17653898

Lynch syndrome in Tunisia: first description of clinical features and germline mutations.

Moussa SA, Moussa A, Kourda N, Mezlini A, Abdelli N, Zerimech F, Najjar T, Jilani SB, Porchet N, Ayed FB, Manai M, Buisine MP.

Int J Colorectal Dis. 2011 Apr;26(4):455-67. doi: 10.1007/s00384-010-1129-9. Epub 2011 Feb 11.

PubMed [citation]

PMID:: 21311894

See all PubMed Citations (5)

Details of each submission

From Ambry Genetics, SCV000580389.6

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

Description

The p.S281* pathogenic mutation (also known as c.842C>G), located in coding exon 5 of the MSH2 gene, results from a C to G substitution at nucleotide position 842. This changes the amino acid from a serine to a stop codon within coding exon 5. This mutation has been identified in multiple colorectal cancer patients who met Amsterdam II and/or Bethesda criteria and whose tumors exhibited absent staining for the MSH2 and MSH6 proteins (Zhu F et al. Hered Cancer Clin Pract, 2019 Mar;17:9; Moussa SA et al. Int J Colorectal Dis. 2011 Apr;26:455-67; Rahner N et al. Acta Oncol, 2007;46:763-9). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.

#	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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