NM_000251.3(MSH2):c.792+1G>A AND Hereditary nonpolyposis colorectal neoplasms

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 5, 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:: RCV001233639.5

Allele description [Variation Report for NM_000251.3(MSH2):c.792+1G>A]

NM_000251.3(MSH2):c.792+1G>A

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.792+1G>A

HGVS:

NC_000002.12:g.47412561G>A
NG_007110.2:g.14438G>A
NM_000251.3:c.792+1G>AMANE SELECT
NM_001258281.1:c.594+1G>A
NM_001406631.1:c.792+1G>A
NM_001406632.1:c.792+1G>A
NM_001406633.1:c.792+1G>A
NM_001406634.1:c.792+1G>A
NM_001406635.1:c.792+1G>A
NM_001406636.1:c.792+1G>A
NM_001406637.1:c.792+1G>A
NM_001406638.1:c.792+1G>A
NM_001406639.1:c.792+1G>A
NM_001406640.1:c.792+1G>A
NM_001406641.1:c.792+1G>A
NM_001406642.1:c.792+1G>A
NM_001406643.1:c.792+1G>A
NM_001406644.1:c.792+1G>A
NM_001406645.1:c.792+1G>A
NM_001406646.1:c.792+1G>A
NM_001406647.1:c.792+1G>A
NM_001406648.1:c.792+1G>A
NM_001406649.1:c.792+1G>A
NM_001406650.1:c.792+1G>A
NM_001406651.1:c.792+1G>A
NM_001406652.1:c.792+1G>A
NM_001406653.1:c.732+1G>A
NM_001406654.1:c.372+1G>A
NM_001406655.1:c.792+1G>A
NM_001406656.1:c.-204+1G>A
NM_001406657.1:c.792+1G>A
NM_001406658.1:c.-527+1G>A
NM_001406659.1:c.-677+1G>A
NM_001406660.1:c.-874+1G>A
NM_001406661.1:c.-829+1G>A
NM_001406662.1:c.-746+1G>A
NM_001406666.1:c.792+1G>A
NM_001406669.1:c.-677+1G>A
NM_001406672.1:c.792+1G>A
NM_001406674.1:c.792+1G>A
LRG_218t1:c.792+1G>A
LRG_218:g.14438G>A
NC_000002.11:g.47639700G>A
NM_000251.1:c.792+1G>A
NM_000251.2:c.792+1G>A

Links:

dbSNP: rs267607934

NCBI 1000 Genomes Browser:

rs267607934

Molecular consequence:

NM_000251.3:c.792+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001258281.1:c.594+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406631.1:c.792+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406632.1:c.792+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406633.1:c.792+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406634.1:c.792+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406635.1:c.792+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406636.1:c.792+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406637.1:c.792+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406638.1:c.792+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406639.1:c.792+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406640.1:c.792+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406641.1:c.792+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406642.1:c.792+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406643.1:c.792+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406644.1:c.792+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406645.1:c.792+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406646.1:c.792+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406647.1:c.792+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406648.1:c.792+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406649.1:c.792+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406650.1:c.792+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406651.1:c.792+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406652.1:c.792+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406653.1:c.732+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406654.1:c.372+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406655.1:c.792+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406656.1:c.-204+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406657.1:c.792+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406658.1:c.-527+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406659.1:c.-677+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406660.1:c.-874+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406661.1:c.-829+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406662.1:c.-746+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406666.1:c.792+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406669.1:c.-677+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406672.1:c.792+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406674.1:c.792+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001406243	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 5, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 15713769, 25117503, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001406243

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 5, 2023)

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

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

High prevalence of mismatch repair deficiency in prostate cancers diagnosed in mismatch repair gene mutation carriers from the colon cancer family registry.

Rosty C, Walsh MD, Lindor NM, Thibodeau SN, Mundt E, Gallinger S, Aronson M, Pollett A, Baron JA, Pearson S, Clendenning M, Walters RJ, Nagler BN, Crawford WJ, Young JP, Winship I, Win AK, Hopper JL, Jenkins MA, Buchanan DD.

Fam Cancer. 2014 Dec;13(4):573-82. doi: 10.1007/s10689-014-9744-1.

PubMed [citation]

PMID:: 25117503
PMCID:: PMC4329248

See all PubMed Citations (3)

Details of each submission

From Invitae, SCV001406243.5

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

Description

This sequence change affects a donor 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. This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individuals with colorectal cancer (PMID: 15713769, 25117503). ClinVar contains an entry for this variant (Variation ID: 91205). Studies have shown that disruption of this splice site results in partial intron inclusion due to the activation of a cryptic splice site and introduces a premature termination codon (Invitae). The resulting mRNA is expected to undergo nonsense-mediated decay. 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: May 7, 2024

ClinVar

Relating variation to medicine