NM_000251.3(MSH2):c.792+1_792+2inv AND Hereditary nonpolyposis colorectal neoplasms

Germline classification:: Pathogenic (1 submission)
Last evaluated:: May 24, 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:: RCV003099786.3

Allele description [Variation Report for NM_000251.3(MSH2):c.792+1_792+2inv]

NM_000251.3(MSH2):c.792+1_792+2inv

Gene:

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

Variant type:

Inversion

Cytogenetic location:

2p21

Genomic location:

Preferred name:

NM_000251.3(MSH2):c.792+1_792+2inv

HGVS:

NC_000002.12:g.47412561_47412562inv
NG_007110.2:g.14438_14439inv
NM_000251.3:c.792+1_792+2invMANE SELECT
NM_001258281.1:c.594+1_594+2inv
LRG_218:g.14438_14439inv
NC_000002.11:g.47639700_47639701delinsAC
NC_000002.11:g.47639700_47639701inv
NM_000251.1:c.792+1_792+2delGTinsAC

Molecular consequence:

NM_000251.3:c.792+1_792+2inv - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001258281.1:c.594+1_594+2inv - splice donor variant - [Sequence Ontology: SO:0001575]

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
SCV003340167	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (May 24, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 11524701, 33468175, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003340167

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(May 24, 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

The frequency of hereditary defective mismatch repair in a prospective series of unselected colorectal carcinomas.

Cunningham JM, Kim CY, Christensen ER, Tester DJ, Parc Y, Burgart LJ, Halling KC, McDonnell SK, Schaid DJ, Walsh Vockley C, Kubly V, Nelson H, Michels VV, Thibodeau SN.

Am J Hum Genet. 2001 Oct;69(4):780-90. Epub 2001 Aug 24. Erratum in: Am J Hum Genet 2001 Nov;69(5):1160.

PubMed [citation]

PMID:: 11524701
PMCID:: PMC1226064

A rare large duplication of MLH1 identified in Lynch syndrome.

Kumar A, Paramasivam N, Bandapalli OR, Schlesner M, Chen T, Sijmons R, Dymerska D, Golebiewska K, Kuswik M, Lubinski J, Hemminki K, Försti A.

Hered Cancer Clin Pract. 2021 Jan 19;19(1):10. doi: 10.1186/s13053-021-00167-0.

PubMed [citation]

PMID:: 33468175
PMCID:: PMC7814444

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003340167.2

#	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 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. Information on the frequency of this variant in the gnomAD database is not available, as this variant may be reported differently in the database. Disruption of this splice site has been observed in individual(s) with clinical features of Lynch syndrome (PMID: 11524701, 33468175). It has also been observed to segregate with disease in related individuals. Studies have shown that disruption of this splice site results in activation of cryptic splice sites 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: Sep 29, 2024

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