NM_000251.3(MSH2):c.2005+255_2089del AND Hereditary nonpolyposis colorectal neoplasms

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 26, 2019
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:: RCV001047717.1

Allele description [Variation Report for NM_000251.3(MSH2):c.2005+255_2089del]

NM_000251.3(MSH2):c.2005+255_2089del

Gene:

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

Variant type:

Deletion

Cytogenetic location:

2p21

Genomic location:

Preferred name:

NM_000251.3(MSH2):c.2005+255_2089del

HGVS:

NC_000002.12:g.47475522_47476447del
NC_000002.12:g.47475525_47476450del
NG_007110.2:g.77402_78327del
NM_000251.3:c.2005+255_2089delMANE SELECT
NM_001258281.1:c.1807+255_1891del
LRG_218t1:c.2005+252_2086del
LRG_218:g.77402_78327del
NC_000002.11:g.47702664_47703589del
NM_000251.2:c.2005+252_2086del

Links:

dbSNP: rs1667266283

NCBI 1000 Genomes Browser:

rs1667266283

Molecular consequence:

NM_000251.3:c.2005+255_2089del - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001258281.1:c.1807+255_1891del - splice acceptor variant - [Sequence Ontology: SO:0001574]

Condition(s)

Name:: Hereditary nonpolyposis colorectal neoplasms
Identifiers:: MeSH: D003123; MedGen: C0009405

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001211696	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 26, 2019)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 23690608, 11606497, 18931482, 26248088, 19731080, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001211696

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 26, 2019)

germline

clinical testing

PubMed (6)
[See all records that cite these PMIDs]

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 screens to identify pathogenic gene variants in the common cancer predisposition Lynch syndrome.

Drost M, Lützen A, van Hees S, Ferreira D, Calléja F, Zonneveld JB, Nielsen FC, Rasmussen LJ, de Wind N.

Proc Natl Acad Sci U S A. 2013 Jun 4;110(23):9403-8. doi: 10.1073/pnas.1220537110. Epub 2013 May 20.

PubMed [citation]

PMID:: 23690608
PMCID:: PMC3677471

The colon cancer burden of genetically defined hereditary nonpolyposis colon cancer.

Samowitz WS, Curtin K, Lin HH, Robertson MA, Schaffer D, Nichols M, Gruenthal K, Leppert MF, Slattery ML.

Gastroenterology. 2001 Oct;121(4):830-8.

PubMed [citation]

PMID:: 11606497

See all PubMed Citations (6)

Details of each submission

From Invitae, SCV001211696.1

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

Description

This variant results in the deletion of part of exon 13 (c.2005+255_2089del) of the MSH2 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant has not been reported in the literature in individuals with MSH2-related conditions. This variant disrupts the p.Gly683 amino acid residue in MSH2. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 11606497, 19731080, 26248088, 23690608, 18931482). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Loss-of-function variants in MSH2 are known to be pathogenic (PMID: 15849733, 24362816). For these reasons, this variant has been classified as Pathogenic.

#	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: Mar 26, 2023

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