NM_000251.3(MSH2):c.1386+1G>A AND Hereditary nonpolyposis colorectal neoplasms

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 28, 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:: RCV000684786.8

Allele description [Variation Report for NM_000251.3(MSH2):c.1386+1G>A]

NM_000251.3(MSH2):c.1386+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.1386+1G>A

HGVS:

NC_000002.12:g.47445658G>A
NG_007110.2:g.47535G>A
NM_000251.3:c.1386+1G>AMANE SELECT
NM_001258281.1:c.1188+1G>A
NM_001406631.1:c.1386+1G>A
NM_001406632.1:c.1386+1G>A
NM_001406633.1:c.1386+1G>A
NM_001406634.1:c.1386+1G>A
NM_001406635.1:c.1386+1G>A
NM_001406636.1:c.1353+1G>A
NM_001406637.1:c.1386+1G>A
NM_001406638.1:c.1386+1G>A
NM_001406639.1:c.1386+1G>A
NM_001406640.1:c.1386+1G>A
NM_001406641.1:c.1386+1G>A
NM_001406642.1:c.1386+1G>A
NM_001406643.1:c.1386+1G>A
NM_001406644.1:c.1386+1G>A
NM_001406645.1:c.1386+1G>A
NM_001406646.1:c.1386+1G>A
NM_001406647.1:c.1236+1G>A
NM_001406648.1:c.1386+1G>A
NM_001406649.1:c.1236+1G>A
NM_001406650.1:c.1236+1G>A
NM_001406651.1:c.1236+1G>A
NM_001406652.1:c.1236+1G>A
NM_001406653.1:c.1326+1G>A
NM_001406654.1:c.966+1G>A
NM_001406655.1:c.1386+1G>A
NM_001406656.1:c.489+1G>A
NM_001406657.1:c.1386+1G>A
NM_001406658.1:c.30+1G>A
NM_001406659.1:c.30+1G>A
NM_001406660.1:c.30+1G>A
NM_001406661.1:c.30+1G>A
NM_001406662.1:c.30+1G>A
NM_001406666.1:c.1386+1G>A
NM_001406669.1:c.30+1G>A
NM_001406672.1:c.1236+1G>A
NM_001406674.1:c.1386+1G>A
LRG_218t1:c.1386+1G>A
LRG_218:g.47535G>A
NC_000002.11:g.47672797G>A
NM_000251.1:c.1386+1G>A
NM_000251.2:c.1386+1G>A

Links:

dbSNP: rs267607957

NCBI 1000 Genomes Browser:

rs267607957

Molecular consequence:

NM_000251.3:c.1386+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001258281.1:c.1188+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406631.1:c.1386+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406632.1:c.1386+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406633.1:c.1386+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406634.1:c.1386+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406635.1:c.1386+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406636.1:c.1353+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406637.1:c.1386+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406638.1:c.1386+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406639.1:c.1386+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406640.1:c.1386+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406641.1:c.1386+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406642.1:c.1386+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406643.1:c.1386+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406644.1:c.1386+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406645.1:c.1386+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406646.1:c.1386+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406647.1:c.1236+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406648.1:c.1386+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406649.1:c.1236+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406650.1:c.1236+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406651.1:c.1236+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406652.1:c.1236+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406653.1:c.1326+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406654.1:c.966+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406655.1:c.1386+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406656.1:c.489+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406657.1:c.1386+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406658.1:c.30+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406659.1:c.30+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406660.1:c.30+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406661.1:c.30+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406662.1:c.30+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406666.1:c.1386+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406669.1:c.30+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406672.1:c.1236+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406674.1:c.1386+1G>A - 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
SCV000253799	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 28, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 15849733, 16736289, 16395668, 19669161, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000253799

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 28, 2023)

germline

clinical testing

PubMed (5)
[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

Spectrum and frequencies of mutations in MSH2 and MLH1 identified in 1,721 German families suspected of hereditary nonpolyposis colorectal cancer.

Mangold E, Pagenstecher C, Friedl W, Mathiak M, Buettner R, Engel C, Loeffler M, Holinski-Feder E, Müller-Koch Y, Keller G, Schackert HK, Krüger S, Goecke T, Moeslein G, Kloor M, Gebert J, Kunstmann E, Schulmann K, Rüschoff J, Propping P.

Int J Cancer. 2005 Sep 20;116(5):692-702.

PubMed [citation]

PMID:: 15849733

Germline mutations of the hMLH1 and hMSH2 mismatch repair genes in Belgian hereditary nonpolyposis colon cancer (HNPCC) patients.

Spaepen M, Vankeirsbilck B, Van Opstal S, Tejpar S, Van Cutsem E, Geboes K, Legius E, Matthijs G.

Fam Cancer. 2006;5(2):179-89.

PubMed [citation]

PMID:: 16736289

See all PubMed Citations (5)

Details of each submission

From Invitae, SCV000253799.11

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This sequence change affects a donor splice site in intron 8 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 individual(s) with Lynch syndrome (PMID: 15849733, 16736289). ClinVar contains an entry for this variant (Variation ID: 90641). Studies have shown that disruption of this splice site results in skipping of exon 8 and introduces a premature termination codon (PMID: 16395668, 19669161; 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: Jun 23, 2024

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