NM_000251.3(MSH2):c.793-2A>G AND Hereditary nonpolyposis colorectal neoplasms

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Aug 20, 2022
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:: RCV001219161.8

Allele description [Variation Report for NM_000251.3(MSH2):c.793-2A>G]

NM_000251.3(MSH2):c.793-2A>G

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.793-2A>G

HGVS:

NC_000002.12:g.47414267A>G
NG_007110.2:g.16144A>G
NM_000251.3:c.793-2A>GMANE SELECT
NM_001258281.1:c.595-2A>G
NM_001406631.1:c.793-2A>G
NM_001406632.1:c.793-2A>G
NM_001406633.1:c.793-2A>G
NM_001406634.1:c.793-2A>G
NM_001406635.1:c.793-2A>G
NM_001406636.1:c.793-35A>G
NM_001406637.1:c.793-2A>G
NM_001406638.1:c.793-2A>G
NM_001406639.1:c.793-2A>G
NM_001406640.1:c.793-2A>G
NM_001406641.1:c.793-2A>G
NM_001406642.1:c.793-2A>G
NM_001406643.1:c.793-2A>G
NM_001406644.1:c.793-2A>G
NM_001406645.1:c.793-2A>G
NM_001406646.1:c.793-2A>G
NM_001406647.1:c.792+1707A>G
NM_001406648.1:c.793-2A>G
NM_001406649.1:c.792+1707A>G
NM_001406650.1:c.792+1707A>G
NM_001406651.1:c.792+1707A>G
NM_001406652.1:c.792+1707A>G
NM_001406653.1:c.733-2A>G
NM_001406654.1:c.373-2A>G
NM_001406655.1:c.793-2A>G
NM_001406656.1:c.-105-2A>G
NM_001406657.1:c.793-2A>G
NM_001406658.1:c.-527+1707A>G
NM_001406659.1:c.-676-2A>G
NM_001406660.1:c.-873-2A>G
NM_001406661.1:c.-828-2A>G
NM_001406662.1:c.-745-2A>G
NM_001406666.1:c.793-2A>G
NM_001406669.1:c.-676-2A>G
NM_001406672.1:c.792+1707A>G
NM_001406674.1:c.793-2A>G
LRG_218t1:c.793-2A>G
LRG_218:g.16144A>G
NC_000002.11:g.47641406A>G
NM_000251.1:c.793-2A>G
NM_000251.2:c.793-2A>G

Links:

dbSNP: rs267607933

NCBI 1000 Genomes Browser:

rs267607933

Molecular consequence:

NM_001406636.1:c.793-35A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001406647.1:c.792+1707A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001406649.1:c.792+1707A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001406650.1:c.792+1707A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001406651.1:c.792+1707A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001406652.1:c.792+1707A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001406658.1:c.-527+1707A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001406672.1:c.792+1707A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_000251.3:c.793-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001258281.1:c.595-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001406631.1:c.793-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001406632.1:c.793-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001406633.1:c.793-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001406634.1:c.793-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001406635.1:c.793-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001406637.1:c.793-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001406638.1:c.793-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001406639.1:c.793-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001406640.1:c.793-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001406641.1:c.793-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001406642.1:c.793-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001406643.1:c.793-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001406644.1:c.793-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001406645.1:c.793-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001406646.1:c.793-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001406648.1:c.793-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001406653.1:c.733-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001406654.1:c.373-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001406655.1:c.793-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001406656.1:c.-105-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001406657.1:c.793-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001406659.1:c.-676-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001406660.1:c.-873-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001406661.1:c.-828-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001406662.1:c.-745-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001406666.1:c.793-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001406669.1:c.-676-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001406674.1:c.793-2A>G - 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
SCV001391083	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Aug 20, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 20052760, 27601186, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001391083

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Aug 20, 2022)

germline

clinical testing

PubMed (3)
[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

Microsatellite instability in the peripheral blood leukocytes of HNPCC patients.

Coolbaugh-Murphy MI, Xu JP, Ramagli LS, Ramagli BC, Brown BW, Lynch PM, Hamilton SR, Frazier ML, Siciliano MJ.

Hum Mutat. 2010 Mar;31(3):317-24. doi: 10.1002/humu.21190.

PubMed [citation]

PMID:: 20052760
PMCID:: PMC3544178

Mismatch repair gene mutation spectrum in the Swedish Lynch syndrome population.

Lagerstedt-Robinson K, Rohlin A, Aravidis C, Melin B, Nordling M, Stenmark-Askmalm M, Lindblom A, Nilbert M.

Oncol Rep. 2016 Nov;36(5):2823-2835. doi: 10.3892/or.2016.5060. Epub 2016 Sep 1.

PubMed [citation]

PMID:: 27601186

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001391083.5

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

Description

For these reasons, this variant has been classified as Pathogenic. Studies have shown that disruption of this splice site results in activation of a cryptic splice site and introduces a premature termination codon (Invitae). The resulting mRNA is expected to undergo nonsense-mediated decay. ClinVar contains an entry for this variant (Variation ID: 947991). Disruption of this splice site has been observed in individuals with Lynch syndrome (PMID: 20052760, 27601186; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change affects an acceptor splice site in intron 4 of the MSH2 gene. RNA analysis indicates that disruption of this splice site induces altered splicing and may result in an absent or disrupted protein product.

#	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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