NM_000251.3(MSH2):c.2041C>T (p.Gln681Ter) AND Hereditary cancer-predisposing syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: May 13, 2021
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:: RCV000491607.4

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 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
SCV000580521	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (May 13, 2021)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 12624141, 24710284 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000580521

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(May 13, 2021)

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

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

Details of each submission

From Ambry Genetics, SCV000580521.6

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

Description

The p.Q681* pathogenic mutation (also known as c.2041C>T), located in coding exon 13 of the MSH2 gene, results from a C to T substitution at nucleotide position 2041. This changes the amino acid from a glutamine to a stop codon within coding exon 13. This alteration has been reported in a French cohort of patients suspected of having HPNCC/Lynch syndrome (Parc Y et al. J. Med. Genet. 2003 Mar;40:208-13). This variant has also been identified in a family meeting Amsterdam criteria (Liu Y et al. PLoSOne. 2014 Apr 7;9(4):e94170). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted 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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