NM_000251.3(MSH2):c.2422G>T (p.Glu808Ter) AND Hereditary cancer-predisposing syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jul 12, 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:: RCV002453386.2

Allele description [Variation Report for NM_000251.3(MSH2):c.2422G>T (p.Glu808Ter)]

NM_000251.3(MSH2):c.2422G>T (p.Glu808Ter)

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.2422G>T (p.Glu808Ter)

HGVS:

NC_000002.12:g.47478483G>T
NG_007110.2:g.80360G>T
NM_000251.3:c.2422G>TMANE SELECT
NM_001258281.1:c.2224G>T
NP_000242.1:p.Glu808Ter
NP_001245210.1:p.Glu742Ter
LRG_218:g.80360G>T
NC_000002.11:g.47705622G>T
NM_000251.1:c.2422G>T

Protein change:

E742*

Links:

dbSNP: rs34986638

NCBI 1000 Genomes Browser:

rs34986638

Molecular consequence:

NM_000251.3:c.2422G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001258281.1:c.2224G>T - 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
SCV002736032	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Jul 12, 2021)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 15520370, 16451135 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002736032

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Jul 12, 2021)

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	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Multiple rare variants in different genes account for multifactorial inherited susceptibility to colorectal adenomas.

Fearnhead NS, Wilding JL, Winney B, Tonks S, Bartlett S, Bicknell DC, Tomlinson IP, Mortensen NJ, Bodmer WF.

Proc Natl Acad Sci U S A. 2004 Nov 9;101(45):15992-7. Epub 2004 Nov 1.

PubMed [citation]

PMID:: 15520370
PMCID:: PMC528777

Germline MSH2 and MLH1 mutational spectrum including large rearrangements in HNPCC families from Poland (update study).

Kurzawski G, Suchy J, Lener M, Kłujszo-Grabowska E, Kładny J, Safranow K, Jakubowska K, Jakubowska A, Huzarski T, Byrski T, Debniak T, Cybulski C, Gronwald J, Oszurek O, Oszutowska D, Kowalska E, Góźdź S, Niepsuj S, Słomski R, Pławski A, Łacka-Wojciechowska A, Rozmiarek A, et al.

Clin Genet. 2006 Jan;69(1):40-7.

PubMed [citation]

PMID:: 16451135

Details of each submission

From Ambry Genetics, SCV002736032.2

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

Description

The p.E808* pathogenic mutation (also known as c.2422G>T), located in coding exon 14 of the MSH2 gene, results from a G to T substitution at nucleotide position 2422. This changes the amino acid from a glutamic acid to a stop codon within coding exon 14. This alteration was identified in an individual diagnosed with multiple colorectal polyps (Fearnhead NS et al. Proc Natl Acad Sci U S A, 2004 Nov;101:15992-7). Additionally, this alteration was identified in an individual meeting clinical criteria for Lynch Syndrome (Kurzawski G et al. Clin Genet, 2006 Jan;69:40-7). 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: May 7, 2024

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