NM_000251.3(MSH2):c.1237C>T (p.Gln413Ter) AND Hereditary cancer-predisposing syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 7, 2018
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:: RCV000490844.2

Allele description [Variation Report for NM_000251.3(MSH2):c.1237C>T (p.Gln413Ter)]

NM_000251.3(MSH2):c.1237C>T (p.Gln413Ter)

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.1237C>T (p.Gln413Ter)

HGVS:

NC_000002.12:g.47429902C>T
NG_007110.2:g.31779C>T
NM_000251.3:c.1237C>TMANE SELECT
NM_001258281.1:c.1039C>T
NP_000242.1:p.Gln413Ter
NP_000242.1:p.Gln413Ter
NP_001245210.1:p.Gln347Ter
LRG_218t1:c.1237C>T
LRG_218:g.31779C>T
LRG_218p1:p.Gln413Ter
NC_000002.11:g.47657041C>T
NM_000251.1:c.1237C>T
NM_000251.2:c.1237C>T
p.Gln413*

Protein change:

Q347*

Links:

dbSNP: rs863225387

NCBI 1000 Genomes Browser:

rs863225387

Molecular consequence:

NM_000251.3:c.1237C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001258281.1:c.1039C>T - nonsense - [Sequence Ontology: SO:0001587]

Observations:

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
SCV000580399	Ambry Genetics	criteria provided, single submitter (Ambry General Variant Classification Scheme_2022)	Pathogenic (Dec 7, 2018)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 20937110, 8952554 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000580399

Ambry Genetics

criteria provided, single submitter

(Ambry General Variant Classification Scheme_2022)

Pathogenic
(Dec 7, 2018)

germline

clinical testing

PubMed (2)
[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	1	not provided	not provided	1	not provided	clinical testing

Citations

PubMed

Screening of the DNA mismatch repair genes MLH1, MSH2 and MSH6 in a Greek cohort of Lynch syndrome suspected families.

Thodi G, Fostira F, Sandaltzopoulos R, Nasioulas G, Grivas A, Boukovinas I, Mylonaki M, Panopoulos C, Magic MB, Fountzilas G, Yannoukakos D.

BMC Cancer. 2010 Oct 11;10:544. doi: 10.1186/1471-2407-10-544.

PubMed [citation]

PMID:: 20937110
PMCID:: PMC2976752

Mutations of the transforming growth factor-beta type II receptor gene are strongly related to sporadic proximal colon carcinomas with microsatellite instability.

Akiyama Y, Iwanaga R, Ishikawa T, Sakamoto K, Nishi N, Nihei Z, Iwama T, Saitoh K, Yuasa Y.

Cancer. 1996 Dec 15;78(12):2478-84.

PubMed [citation]

PMID:: 8952554

Details of each submission

From Ambry Genetics, SCV000580399.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (2)

Description

The p.Q413* pathogenic mutation (also known as c.1237C>T), located in coding exon 7 of the MSH2 gene, results from a C to T substitution at nucleotide position 1237. This changes the amino acid from a glutamine to a stop codon within coding exon 7. This mutation was described in a family meeting Amsterdam II criteria, in which the proband had a personal history of endometrial cancer, and family history was significant for endometrial, colorectal, and stomach cancer (Thodi G et al. BMC Cancer 2010 Oct;10:544). 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	1	not provided	not provided		1	not provided	not provided	not provided

Last Updated: Feb 20, 2024

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