NM_000251.3(MSH2):c.1035G>A (p.Trp345Ter) AND Hereditary cancer-predisposing syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Mar 30, 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:: RCV000492045.5

Allele description [Variation Report for NM_000251.3(MSH2):c.1035G>A (p.Trp345Ter)]

NM_000251.3(MSH2):c.1035G>A (p.Trp345Ter)

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.1035G>A (p.Trp345Ter)

HGVS:

NC_000002.12:g.47416388G>A
NG_007110.2:g.18265G>A
NM_000251.3:c.1035G>AMANE SELECT
NM_001258281.1:c.837G>A
NP_000242.1:p.Trp345Ter
NP_000242.1:p.Trp345Ter
NP_001245210.1:p.Trp279Ter
LRG_218t1:c.1035G>A
LRG_218:g.18265G>A
LRG_218p1:p.Trp345Ter
NC_000002.11:g.47643527G>A
NM_000251.1:c.1035G>A
NM_000251.2:c.1035G>A

Protein change:

W279*

Links:

dbSNP: rs63750396

NCBI 1000 Genomes Browser:

rs63750396

Molecular consequence:

NM_000251.3:c.1035G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001258281.1:c.837G>A - 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

Recent activity

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cytochrome oxidase subunit I, partial (mitochondrion) [Callinectes sp. GI05]
cytochrome oxidase subunit I, partial (mitochondrion) [Callinectes sp. GI05]
gi|1720642322|gb|QEA03552.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000580470	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Mar 30, 2023)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 14970868, 15713769, 19419416, 25525159, 28127413, 28577310 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000580470

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Mar 30, 2023)

germline

clinical testing

PubMed (6)
[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

Genetic testing among high-risk individuals in families with hereditary nonpolyposis colorectal cancer.

Ponz de Leon M, Benatti P, Di Gregorio C, Pedroni M, Losi L, Genuardi M, Viel A, Fornasarig M, Lucci-Cordisco E, Anti M, Ponti G, Borghi F, Lamberti I, Roncucci L.

Br J Cancer. 2004 Feb 23;90(4):882-7.

PubMed [citation]

PMID:: 14970868
PMCID:: PMC2410159

Conversion analysis for mutation detection in MLH1 and MSH2 in patients with colorectal cancer.

Casey G, Lindor NM, Papadopoulos N, Thibodeau SN, Moskow J, Steelman S, Buzin CH, Sommer SS, Collins CE, Butz M, Aronson M, Gallinger S, Barker MA, Young JP, Jass JR, Hopper JL, Diep A, Bapat B, Salem M, Seminara D, Haile R; Colon Cancer Family Registry..

JAMA. 2005 Feb 16;293(7):799-809.

PubMed [citation]

PMID:: 15713769
PMCID:: PMC2933041

See all PubMed Citations (6)

Details of each submission

From Ambry Genetics, SCV000580470.7

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

The p.W345* pathogenic mutation (also known as c.1035G>A), located in coding exon 6 of the MSH2 gene, results from a G to A substitution at nucleotide position 1035. This changes the amino acid from a tryptophan to a stop codon within coding exon 6. This alteration has been reported in multiple individuals with personal and/or family histories consistent with Lynch syndrome (Ponz de Leon M et al, Br. J. Cancer 2004 Feb; 90(4):882-7; Tang R, Clin. Genet. 2009 Apr; 75(4):334-45). In addition, an alteration resulting in the same amino acid change and stop codon, p.W345* (c.1034G>A) has been reported in a HNPCC-like family with loss of expression of MSH2 on IHC (Casey G et al, JAMA 2005 Feb; 293(7):799-809). 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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