NM_000251.3(MSH2):c.2041C>T (p.Gln681Ter) AND Hereditary nonpolyposis colorectal neoplasms

Germline classification:: Pathogenic (1 submission)
Last evaluated:: May 23, 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:: RCV000541933.6

Allele description [Variation Report for NM_000251.3(MSH2):c.2041C>T (p.Gln681Ter)]

NM_000251.3(MSH2):c.2041C>T (p.Gln681Ter)

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.2041C>T (p.Gln681Ter)

HGVS:

NC_000002.12:g.47476402C>T
NG_007110.2:g.78279C>T
NM_000251.3:c.2041C>TMANE SELECT
NM_001258281.1:c.1843C>T
NP_000242.1:p.Gln681Ter
NP_000242.1:p.Gln681Ter
NP_001245210.1:p.Gln615Ter
LRG_218t1:c.2041C>T
LRG_218:g.78279C>T
LRG_218p1:p.Gln681Ter
NC_000002.11:g.47703541C>T
NM_000251.1:c.2041C>T
NM_000251.2:c.2041C>T

Protein change:

Q615*

Links:

dbSNP: rs730881762

NCBI 1000 Genomes Browser:

rs730881762

Molecular consequence:

NM_000251.3:c.2041C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001258281.1:c.1843C>T - nonsense - [Sequence Ontology: SO:0001587]

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
SCV000625340	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (May 23, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 12624141, 24710284, 15849733, 24362816, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000625340

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(May 23, 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

Cancer risk in 348 French MSH2 or MLH1 gene carriers.

Parc Y, Boisson C, Thomas G, Olschwang S.

J Med Genet. 2003 Mar;40(3):208-13. No abstract available.

PubMed [citation]

PMID:: 12624141
PMCID:: PMC1735402

Systematic study on genetic and epimutational profile of a cohort of Amsterdam criteria-defined Lynch Syndrome in Singapore.

Liu Y, Chew MH, Goh XW, Tan SY, Loi CT, Tan YM, Law HY, Koh PK, Tang CL.

PLoS One. 2014;9(4):e94170. doi: 10.1371/journal.pone.0094170.

PubMed [citation]

PMID:: 24710284
PMCID:: PMC3978005

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000625340.5

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

Description

For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 428498). This premature translational stop signal has been observed in individual(s) with hereditary non-polyposis colorectal cancer (PMID: 12624141, 24710284). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gln681*) in the MSH2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MSH2 are known to be pathogenic (PMID: 15849733, 24362816).

#	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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