NM_000251.3(MSH2):c.174dup (p.Lys59fs) AND Hereditary nonpolyposis colorectal neoplasms

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jun 9, 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:: RCV001875977.6

Allele description [Variation Report for NM_000251.3(MSH2):c.174dup (p.Lys59fs)]

NM_000251.3(MSH2):c.174dup (p.Lys59fs)

Gene:

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

Variant type:

Duplication

Cytogenetic location:

2p21

Genomic location:

Preferred name:

NM_000251.3(MSH2):c.174dup (p.Lys59fs)

HGVS:

NC_000002.12:g.47403365dup
NG_007110.2:g.5242dup
NM_000251.3:c.174dupMANE SELECT
NM_001258281.1:c.-25dup
NP_000242.1:p.Lys59fs
LRG_218t1:c.174dup
LRG_218:g.5242dup
NC_000002.11:g.47630503_47630504insC
NC_000002.11:g.47630504dup
NC_000002.12:g.47403364_47403365insC
NM_000251.1:c.174dupC
NM_000251.2:c.174dup

Protein change:

K59fs

Links:

dbSNP: rs1672250622

NCBI 1000 Genomes Browser:

rs1672250622

Molecular consequence:

NM_001258281.1:c.-25dup - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_000251.3:c.174dup - 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
SCV002242811	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jun 9, 2021)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 21681552, 28874130, 15849733, 24362816, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002242811

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jun 9, 2021)

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

Characterization of germline mutations of MLH1 and MSH2 in unrelated south American suspected Lynch syndrome individuals.

Valentin MD, da Silva FC, dos Santos EM, Lisboa BG, de Oliveira LP, Ferreira Fde O, Gomy I, Nakagawa WT, Aguiar Junior S, Redal M, Vaccaro C, Valle AD, Sarroca C, Carraro DM, Rossi BM.

Fam Cancer. 2011 Dec;10(4):641-7. doi: 10.1007/s10689-011-9461-y.

PubMed [citation]

PMID:: 21681552

A survey of the clinicopathological and molecular characteristics of patients with suspected Lynch syndrome in Latin America.

Rossi BM, Palmero EI, López-Kostner F, Sarroca C, Vaccaro CA, Spirandelli F, Ashton-Prolla P, Rodriguez Y, de Campos Reis Galvão H, Reis RM, Escremim de Paula A, Capochin Romagnolo LG, Alvarez K, Della Valle A, Neffa F, Kalfayan PG, Spirandelli E, Chialina S, Gutiérrez Angulo M, Castro-Mujica MDC, Sanchez de Monte J, Quispe R, et al.

BMC Cancer. 2017 Sep 5;17(1):623. doi: 10.1186/s12885-017-3599-4.

PubMed [citation]

PMID:: 28874130
PMCID:: PMC5586063

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002242811.3

#	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. This variant has been observed in individual(s) with Lynch syndrome (PMID: 21681552, 28874130). ClinVar contains an entry for this variant (Variation ID: 921072). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Lys59Glnfs*23) 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: Sep 29, 2024

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