NM_000251.3(MSH2):c.942+1G>A AND Hereditary cancer-predisposing syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Apr 29, 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:: RCV001019333.3

Allele description [Variation Report for NM_000251.3(MSH2):c.942+1G>A]

NM_000251.3(MSH2):c.942+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.942+1G>A

HGVS:

NC_000002.12:g.47414419G>A
NG_007110.2:g.16296G>A
NM_000251.3:c.942+1G>AMANE SELECT
NM_001258281.1:c.744+1G>A
NM_001406631.1:c.942+1G>A
NM_001406632.1:c.942+1G>A
NM_001406633.1:c.942+1G>A
NM_001406634.1:c.942+1G>A
NM_001406635.1:c.942+1G>A
NM_001406636.1:c.909+1G>A
NM_001406637.1:c.942+1G>A
NM_001406638.1:c.942+1G>A
NM_001406639.1:c.942+1G>A
NM_001406640.1:c.942+1G>A
NM_001406641.1:c.942+1G>A
NM_001406642.1:c.942+1G>A
NM_001406643.1:c.942+1G>A
NM_001406644.1:c.942+1G>A
NM_001406645.1:c.942+1G>A
NM_001406646.1:c.942+1G>A
NM_001406647.1:c.792+1859G>A
NM_001406648.1:c.942+1G>A
NM_001406649.1:c.792+1859G>A
NM_001406650.1:c.792+1859G>A
NM_001406651.1:c.792+1859G>A
NM_001406652.1:c.792+1859G>A
NM_001406653.1:c.882+1G>A
NM_001406654.1:c.522+1G>A
NM_001406655.1:c.942+1G>A
NM_001406656.1:c.45+1G>A
NM_001406657.1:c.942+1G>A
NM_001406658.1:c.-527+1859G>A
NM_001406659.1:c.-527+1G>A
NM_001406660.1:c.-724+1G>A
NM_001406661.1:c.-679+1G>A
NM_001406662.1:c.-596+1G>A
NM_001406666.1:c.942+1G>A
NM_001406669.1:c.-527+1G>A
NM_001406672.1:c.792+1859G>A
NM_001406674.1:c.942+1G>A
LRG_218t1:c.942+1G>A
LRG_218:g.16296G>A
NC_000002.11:g.47641558G>A
NM_000251.1:c.942+1G>A
NM_000251.2:c.942+1G>A

Links:

dbSNP: rs587779193

NCBI 1000 Genomes Browser:

rs587779193

Molecular consequence:

NM_001406647.1:c.792+1859G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001406649.1:c.792+1859G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001406650.1:c.792+1859G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001406651.1:c.792+1859G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001406652.1:c.792+1859G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001406658.1:c.-527+1859G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001406672.1:c.792+1859G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_000251.3:c.942+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001258281.1:c.744+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406631.1:c.942+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406632.1:c.942+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406633.1:c.942+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406634.1:c.942+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406635.1:c.942+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406636.1:c.909+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406637.1:c.942+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406638.1:c.942+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406639.1:c.942+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406640.1:c.942+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406641.1:c.942+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406642.1:c.942+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406643.1:c.942+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406644.1:c.942+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406645.1:c.942+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406646.1:c.942+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406648.1:c.942+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406653.1:c.882+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406654.1:c.522+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406655.1:c.942+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406656.1:c.45+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406657.1:c.942+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406659.1:c.-527+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406660.1:c.-724+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406661.1:c.-679+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406662.1:c.-596+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406666.1:c.942+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406669.1:c.-527+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406674.1:c.942+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Name:: Hereditary cancer-predisposing syndrome
Synonyms:: Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001180677	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Apr 29, 2019)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 11048710, 17531815 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001180677

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Apr 29, 2019)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link

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

Crystal structures of mismatch repair protein MutS and its complex with a substrate DNA.

Obmolova G, Ban C, Hsieh P, Yang W.

Nature. 2000 Oct 12;407(6805):703-10.

PubMed [citation]

PMID:: 11048710

Structure of the human MutSalpha DNA lesion recognition complex.

Warren JJ, Pohlhaus TJ, Changela A, Iyer RR, Modrich PL, Beese LS.

Mol Cell. 2007 May 25;26(4):579-92.

PubMed [citation]

PMID:: 17531815

Details of each submission

From Ambry Genetics, SCV001180677.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

The c.942+1G>A intronic pathogenic mutation results from a G to A substitution one nucleotide after coding exon 5 of the MSH2 gene. This nucleotide position is highly conserved in available vertebrate species. Using two different splice site prediction tools, this alteration is predicted by BDGP to abolish the native splice donor site, but is predicted to weaken (but not abolish) the efficiency of the native splice donor site by ESEfinder; however, direct evidence is unavailable. Alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. As such, this alteration is classified as a disease-causing mutation.

#	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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