NM_000251.3(MSH2):c.1885C>T (p.Gln629Ter) AND Hereditary nonpolyposis colon cancer

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 24, 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:: RCV003478996.1

Allele description [Variation Report for NM_000251.3(MSH2):c.1885C>T (p.Gln629Ter)]

NM_000251.3(MSH2):c.1885C>T (p.Gln629Ter)

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.1885C>T (p.Gln629Ter)

HGVS:

NC_000002.12:g.47475150C>T
NG_007110.2:g.77027C>T
NM_000251.3:c.1885C>TMANE SELECT
NM_001258281.1:c.1687C>T
NP_000242.1:p.Gln629Ter
NP_000242.1:p.Gln629Ter
NP_001245210.1:p.Gln563Ter
LRG_218t1:c.1885C>T
LRG_218:g.77027C>T
LRG_218p1:p.Gln629Ter
NC_000002.11:g.47702289C>T
NM_000251.1:c.1885C>T
NM_000251.2:c.1885C>T

Protein change:

Q563*

Links:

dbSNP: rs63750203

NCBI 1000 Genomes Browser:

rs63750203

Molecular consequence:

NM_000251.3:c.1885C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001258281.1:c.1687C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Hereditary nonpolyposis colon cancer (HNPCC)
Synonyms:: Hereditary nonpolyposis colorectal cancer; Familial nonpolyposis colon cancer; Hereditary Nonpolyposis Colorectal Cancer Syndrome
Identifiers:: MONDO: MONDO:0018630; MedGen: C1333990; OMIM: PS120435

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004223145	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Pathogenic (Nov 24, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004223145

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Pathogenic
(Nov 24, 2023)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

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

Clinical characteristics of patients with colorectal cancer with double somatic mismatch repair mutations compared with Lynch syndrome.

Pearlman R, Haraldsdottir S, de la Chapelle A, Jonasson JG, Liyanarachchi S, Frankel WL, Rafnar T, Stefansson K, Pritchard CC, Hampel H.

J Med Genet. 2019 Jul;56(7):462-470. doi: 10.1136/jmedgenet-2018-105698. Epub 2019 Mar 15.

PubMed [citation]

PMID:: 30877237
PMCID:: PMC6748629

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV004223145.1

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

Description

Variant summary: MSH2 c.1885C>T (p.Gln629X) results in a premature termination codon and is expected to cause absence of the protein due to nonsense mediated decay, a commonly known mechanism for disease. The variant was absent in 251464 control chromosomes (gnomAD). c.1885C>T has been reported in the literature in at least one individual affected with Lynch Syndrome/Hereditary Nonpolyposis Colorectal Cancer (e.g. Pearlman_2019). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication has been ascertained in the context of this evaluation (PMID: 30877237). Two submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. Both submitters classified the variant as pathogenic. Based on the evidence outlined above, the variant was 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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