NM_000251.3(MSH2):c.186_187dup (p.Val63fs) AND Hereditary cancer-predisposing syndrome

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 18, 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:: RCV000491030.2

Allele description

NM_000251.3(MSH2):c.186_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.186_187dup (p.Val63fs)

HGVS:

NC_000002.12:g.47403377_47403378dup
NG_007110.2:g.5254_5255dup
NM_000251.3:c.186_187dupMANE SELECT
NM_001258281.1:c.-13_-12dup
NP_000242.1:p.Val63fs
LRG_218:g.5254_5255dup
NC_000002.11:g.47630512_47630513insGG
NC_000002.11:g.47630516_47630517dup
NM_000251.1:c.186_187dup
NM_000251.1:c.186_187dupGG

Protein change:

V63fs

Links:

dbSNP: rs63750160

NCBI 1000 Genomes Browser:

rs63750160

Molecular consequence:

NM_001258281.1:c.-13_-12dup - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_000251.3:c.186_187dup - frameshift variant - [Sequence Ontology: SO:0001589]

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
SCV000580408	Ambry Genetics	criteria provided, single submitter (Ambry General Variant Classification Scheme_2022)	Pathogenic (Jan 18, 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

SCV000580408

Ambry Genetics

criteria provided, single submitter

(Ambry General Variant Classification Scheme_2022)

Pathogenic
(Jan 18, 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

Targeted next-generation sequencing of 22 mismatch repair genes identifies Lynch syndrome families.

Talseth-Palmer BA, Bauer DC, Sjursen W, Evans TJ, McPhillips M, Proietto A, Otton G, Spigelman AD, Scott RJ.

Cancer Med. 2016 May;5(5):929-41. doi: 10.1002/cam4.628. Epub 2016 Jan 25.

PubMed [citation]

PMID:: 26811195
PMCID:: PMC4864822

Details of each submission

From Ambry Genetics, SCV000580408.5

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

Description

The c.186_187dupGG pathogenic mutation, located in coding exon 1 of the MSH2 gene, results from a duplication of GG at nucleotide positions 186 to 187, causing a translational frameshift with a predicted alternate stop codon (p.V63Gfs*2). This mutation has been reported in an individual who was diagnosed with colorectal cancer at age 51 as well as endometrial cancer (Talseth-Palmer BA et al. Cancer Med, 2016 May;5:929-41). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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: Feb 20, 2024

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