NM_000251.3(MSH2):c.2680dup (p.Met894fs) AND Hereditary nonpolyposis colorectal neoplasms

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 21, 2024
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:: RCV000810344.7

Allele description [Variation Report for NM_000251.3(MSH2):c.2680dup (p.Met894fs)]

NM_000251.3(MSH2):c.2680dup (p.Met894fs)

Gene:

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

Variant type:

Duplication

Cytogenetic location:

2p21

Genomic location:

Preferred name:

NM_000251.3(MSH2):c.2680dup (p.Met894fs)

Other names:

p.Met894AsnfsX5

HGVS:

NC_000002.11:g.47709960_47709961insA
NC_000002.12:g.47482824dup
NG_007110.2:g.84701dup
NM_000251.3:c.2680dupMANE SELECT
NM_001258281.1:c.2482dup
NP_000242.1:p.Met894fs
NP_001245210.1:p.Met828fs
LRG_218:g.84701dup
NC_000002.11:g.47709960_47709961insA
NC_000002.11:g.47709963_47709964insA
NC_000002.11:g.47709963dup
NC_000002.12:g.47482824_47482825insA
NM_000251.1:c.2680dupA
NM_000251.2:c.2680dupA
NM_000251.3:c.2680dupAMANE SELECT

Protein change:

M828fs

Links:

dbSNP: rs876658211

NCBI 1000 Genomes Browser:

rs876658211

Molecular consequence:

NM_000251.3:c.2680dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001258281.1:c.2482dup - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Hereditary nonpolyposis colorectal neoplasms
Identifiers:: MeSH: D003123; MedGen: C0009405

Recent activity

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Homo sapiens junctional adhesion molecule 2 (JAM2), transcript variant 1, mRNA
Homo sapiens junctional adhesion molecule 2 (JAM2), transcript variant 1, mRNA
gi|1519244881|ref|NM_021219.4|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000950540	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 21, 2024)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 27601186, 28514183, 30322717, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000950540

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 21, 2024)

germline

clinical testing

PubMed (4)
[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

Mismatch repair gene mutation spectrum in the Swedish Lynch syndrome population.

Lagerstedt-Robinson K, Rohlin A, Aravidis C, Melin B, Nordling M, Stenmark-Askmalm M, Lindblom A, Nilbert M.

Oncol Rep. 2016 Nov;36(5):2823-2835. doi: 10.3892/or.2016.5060. Epub 2016 Sep 1.

PubMed [citation]

PMID:: 27601186

Multigene Panel Testing Provides a New Perspective on Lynch Syndrome.

Espenschied CR, LaDuca H, Li S, McFarland R, Gau CL, Hampel H.

J Clin Oncol. 2017 Aug 1;35(22):2568-2575. doi: 10.1200/JCO.2016.71.9260. Epub 2017 May 17.

PubMed [citation]

PMID:: 28514183
PMCID:: PMC7186580

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000950540.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This sequence change creates a premature translational stop signal (p.Met894Asnfs*5) in the MSH2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 41 amino acid(s) of the MSH2 protein. This variant is present in population databases (rs756190190, gnomAD 0.003%). This premature translational stop signal has been observed in individuals with clinical features of Lynch syndrome (PMID: 27601186, 28514183, 30322717; external communication). ClinVar contains an entry for this variant (Variation ID: 229809). RNA analysis performed to evaluate the impact of this premature translational stop signal on mRNA splicing indicates it does not significantly alter splicing (Invitae). For these reasons, this variant has been 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: Oct 26, 2024

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