NM_000251.3(MSH2):c.867dup (p.Glu290Ter) AND Hereditary cancer-predisposing syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Sep 28, 2020
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:: RCV002373363.2

Allele description [Variation Report for NM_000251.3(MSH2):c.867dup (p.Glu290Ter)]

NM_000251.3(MSH2):c.867dup (p.Glu290Ter)

Gene:

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

Variant type:

Duplication

Cytogenetic location:

2p21

Genomic location:

Preferred name:

NM_000251.3(MSH2):c.867dup (p.Glu290Ter)

HGVS:

NC_000002.12:g.47414343dup
NG_007110.2:g.16220dup
NM_000251.3:c.867dupMANE SELECT
NM_001258281.1:c.669dup
NM_001406631.1:c.867dup
NM_001406632.1:c.867dup
NM_001406633.1:c.867dup
NM_001406634.1:c.867dup
NM_001406635.1:c.867dup
NM_001406636.1:c.834dup
NM_001406637.1:c.867dup
NM_001406638.1:c.867dup
NM_001406639.1:c.867dup
NM_001406640.1:c.867dup
NM_001406641.1:c.867dup
NM_001406642.1:c.867dup
NM_001406643.1:c.867dup
NM_001406644.1:c.867dup
NM_001406645.1:c.867dup
NM_001406646.1:c.867dup
NM_001406648.1:c.867dup
NM_001406653.1:c.807dup
NM_001406654.1:c.447dup
NM_001406655.1:c.867dup
NM_001406656.1:c.-31dup
NM_001406657.1:c.867dup
NM_001406659.1:c.-602dup
NM_001406660.1:c.-799dup
NM_001406661.1:c.-754dup
NM_001406662.1:c.-671dup
NM_001406666.1:c.867dup
NM_001406669.1:c.-602dup
NM_001406674.1:c.867dup
NP_000242.1:p.Glu290Ter
NP_000242.1:p.Glu290Terfs
NP_001245210.1:p.Glu224Ter
NP_001393560.1:p.Glu290Terfs
NP_001393561.1:p.Glu290Terfs
NP_001393562.1:p.Glu290Terfs
NP_001393563.1:p.Glu290Terfs
NP_001393564.1:p.Glu290Terfs
NP_001393565.1:p.Glu279Terfs
NP_001393566.1:p.Glu290Terfs
NP_001393567.1:p.Glu290Terfs
NP_001393568.1:p.Glu290Terfs
NP_001393569.1:p.Glu290Terfs
NP_001393570.1:p.Glu290Terfs
NP_001393571.1:p.Glu290Terfs
NP_001393572.1:p.Glu290Terfs
NP_001393573.1:p.Glu290Terfs
NP_001393574.1:p.Glu290Terfs
NP_001393575.1:p.Glu290Terfs
NP_001393577.1:p.Glu290Terfs
NP_001393582.1:p.Glu270Terfs
NP_001393583.1:p.Glu150Terfs
NP_001393584.1:p.Glu290Terfs
NP_001393586.1:p.Glu290Terfs
NP_001393595.1:p.Glu290Terfs
NP_001393603.1:p.Glu290Terfs
LRG_218t1:c.867dup
LRG_218:g.16220dup
LRG_218p1:p.Glu290Terfs
NC_000002.11:g.47641482dup
NM_000251.1:c.867dupT
NM_000251.2:c.867dup
NR_176230.1:n.903dup
NR_176231.1:n.903dup
NR_176232.1:n.903dup
NR_176234.1:n.903dup
NR_176235.1:n.903dup
NR_176236.1:n.903dup
NR_176237.1:n.903dup
NR_176238.1:n.903dup
NR_176239.1:n.903dup
NR_176240.1:n.903dup
NR_176241.1:n.903dup
NR_176242.1:n.903dup
NR_176244.1:n.903dup
NR_176245.1:n.903dup
NR_176246.1:n.903dup
NR_176247.1:n.903dup
NR_176248.1:n.903dup
NR_176249.1:n.903dup

Protein change:

E224*

Molecular consequence:

NM_001406631.1:c.867dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406632.1:c.867dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406633.1:c.867dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406634.1:c.867dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406635.1:c.867dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406636.1:c.834dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406637.1:c.867dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406638.1:c.867dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406639.1:c.867dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406640.1:c.867dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406641.1:c.867dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406642.1:c.867dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406643.1:c.867dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406644.1:c.867dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406645.1:c.867dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406646.1:c.867dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406648.1:c.867dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406653.1:c.807dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406654.1:c.447dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406655.1:c.867dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406657.1:c.867dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406666.1:c.867dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406674.1:c.867dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_000251.3:c.867dup - nonsense - [Sequence Ontology: SO:0001587]
NM_001258281.1:c.669dup - nonsense - [Sequence Ontology: SO:0001587]
NM_001406631.1:c.867dup - nonsense - [Sequence Ontology: SO:0001587]
NM_001406632.1:c.867dup - nonsense - [Sequence Ontology: SO:0001587]
NM_001406633.1:c.867dup - nonsense - [Sequence Ontology: SO:0001587]
NM_001406634.1:c.867dup - nonsense - [Sequence Ontology: SO:0001587]
NM_001406635.1:c.867dup - nonsense - [Sequence Ontology: SO:0001587]
NM_001406636.1:c.834dup - nonsense - [Sequence Ontology: SO:0001587]
NM_001406637.1:c.867dup - nonsense - [Sequence Ontology: SO:0001587]
NM_001406638.1:c.867dup - nonsense - [Sequence Ontology: SO:0001587]
NM_001406639.1:c.867dup - nonsense - [Sequence Ontology: SO:0001587]
NM_001406640.1:c.867dup - nonsense - [Sequence Ontology: SO:0001587]
NM_001406641.1:c.867dup - nonsense - [Sequence Ontology: SO:0001587]
NM_001406642.1:c.867dup - nonsense - [Sequence Ontology: SO:0001587]
NM_001406643.1:c.867dup - nonsense - [Sequence Ontology: SO:0001587]
NM_001406644.1:c.867dup - nonsense - [Sequence Ontology: SO:0001587]
NM_001406645.1:c.867dup - nonsense - [Sequence Ontology: SO:0001587]
NM_001406646.1:c.867dup - nonsense - [Sequence Ontology: SO:0001587]
NM_001406648.1:c.867dup - nonsense - [Sequence Ontology: SO:0001587]
NM_001406653.1:c.807dup - nonsense - [Sequence Ontology: SO:0001587]
NM_001406654.1:c.447dup - nonsense - [Sequence Ontology: SO:0001587]
NM_001406655.1:c.867dup - nonsense - [Sequence Ontology: SO:0001587]
NM_001406657.1:c.867dup - nonsense - [Sequence Ontology: SO:0001587]
NM_001406666.1:c.867dup - nonsense - [Sequence Ontology: SO:0001587]
NM_001406674.1:c.867dup - 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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PREDICTED: kin of IRRE-like protein 3, partial [Balearica regulorum gibbericeps]
PREDICTED: kin of IRRE-like protein 3, partial [Balearica regulorum gibbericeps]
gi|723574755|ref|XP_010307361.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002685781	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Sep 28, 2020)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 21387278, 24278394, 29025352 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002685781

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Sep 28, 2020)

germline

clinical testing

PubMed (3)
[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

Analysis of telomere dynamics in peripheral blood cells from patients with Lynch syndrome.

Bozzao C, Lastella P, Ponz de Leon M, Pedroni M, Di Gregorio C, D'Ovidio FD, Resta N, Prete F, Guanti G, Stella A.

Cancer. 2011 Sep 15;117(18):4325-35. doi: 10.1002/cncr.26022. Epub 2011 Mar 8.

PubMed [citation]

PMID:: 21387278

Integrative analysis of hereditary nonpolyposis colorectal cancer: the contribution of allele-specific expression and other assays to diagnostic algorithms.

De Lellis L, Aceto GM, Curia MC, Catalano T, Mammarella S, Veschi S, Fantini F, Battista P, Stigliano V, Messerini L, Mareni C, Sala P, Bertario L, Radice P, Cama A.

PLoS One. 2013;8(11):e81194. doi: 10.1371/journal.pone.0081194.

PubMed [citation]

PMID:: 24278394
PMCID:: PMC3835792

See all PubMed Citations (3)

Details of each submission

From Ambry Genetics, SCV002685781.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

The c.867dupT pathogenic mutation, located in coding exon 5 of the MSH2 gene, results from a duplication of T at nucleotide position 867, causing a translational frameshift with a predicted alternate stop codon (p.E290*). A missense alteration (c.868G>T) resulting in the same premature stop codon (p.E290*) has been reported in individuals with Lynch syndrome (Ponz de Leon M et al. Scand. J. Gastroenterol., 2018 Jan;53:31-37; Bozzao C et al. Cancer, 2011 Sep;117:4325-35), including one patient meeting Amsterdam II criteria whose tumor showed loss of MSH2 by IHC (De Lellis L et al. PLoS ONE, 2013 Nov;8:e81194). 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 1, 2024

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