NM_000251.3(MSH2):c.187dup (p.Val63fs) AND Hereditary nonpolyposis colorectal neoplasms

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jun 20, 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:: RCV003593897.2

Allele description [Variation Report for NM_000251.3(MSH2):c.187dup (p.Val63fs)]

NM_000251.3(MSH2):c.187dup (p.Val63fs)

Gene:

MSH2:mutS homolog 2 [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

2p21

Genomic location:

Preferred name:

NM_000251.3(MSH2):c.187dup (p.Val63fs)

HGVS:

NC_000002.12:g.47403378dup
NG_007110.2:g.5255dup
NM_000251.3:c.187dupMANE SELECT
NM_001258281.1:c.-12dup
NP_000242.1:p.Val63fs
LRG_218:g.5255dup
NC_000002.11:g.47630512_47630513insG
NC_000002.11:g.47630517dup
NM_000251.1:c.187dup
NM_000251.1:c.187dupG

Protein change:

V63fs

Links:

dbSNP: rs63750160

NCBI 1000 Genomes Browser:

rs63750160

Molecular consequence:

NM_001258281.1:c.-12dup - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_000251.3:c.187dup - frameshift variant - [Sequence Ontology: SO:0001589]

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
SCV004292473	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jun 20, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 11393127, 31615790, 15849733, 24362816, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004292473

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jun 20, 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

Hereditary nonpolyposis colorectal cancer with gynecologic malignancies: report of two families in Taiwan.

Chen CH, Huang RL, Yu MS, Wong LJ, Chao TF, Chu TY.

J Formos Med Assoc. 2001 Apr;100(4):269-73.

PubMed [citation]

PMID:: 11393127

Clinical Factors Associated with Urinary Tract Cancer in Individuals with Lynch Syndrome.

Wischhusen JW, Ukaegbu C, Dhingra TG, Uno H, Kastrinos F, Syngal S, Yurgelun MB.

Cancer Epidemiol Biomarkers Prev. 2020 Jan;29(1):193-199. doi: 10.1158/1055-9965.EPI-19-0213. Epub 2019 Oct 15.

PubMed [citation]

PMID:: 31615790
PMCID:: PMC6954282

See all PubMed Citations (5)

Details of each submission

From Invitae, SCV004292473.1

#	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: 90809). This variant is also known as G5 to G6 frame-shift at 183‚Äì187. This premature translational stop signal has been observed in individual(s) with clinical features of Lynch syndrome (PMID: 11393127, 31615790). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Val63Glyfs*19) 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: Jun 23, 2024

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