NM_000251.3(MSH2):c.193A>T (p.Lys65Ter) AND MSH2-related disorder

Germline classification:: Likely pathogenic (1 submission)
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:: RCV004545838.1

Allele description [Variation Report for NM_000251.3(MSH2):c.193A>T (p.Lys65Ter)]

NM_000251.3(MSH2):c.193A>T (p.Lys65Ter)

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.193A>T (p.Lys65Ter)

HGVS:

NC_000002.12:g.47403384A>T
NG_007110.2:g.5261A>T
NG_095167.1:g.588A>T
NM_000251.3:c.193A>TMANE SELECT
NM_001258281.1:c.-6A>T
NM_001406631.1:c.193A>T
NM_001406632.1:c.193A>T
NM_001406633.1:c.193A>T
NM_001406634.1:c.193A>T
NM_001406635.1:c.193A>T
NM_001406636.1:c.193A>T
NM_001406637.1:c.193A>T
NM_001406638.1:c.193A>T
NM_001406639.1:c.193A>T
NM_001406640.1:c.193A>T
NM_001406641.1:c.193A>T
NM_001406642.1:c.193A>T
NM_001406643.1:c.193A>T
NM_001406644.1:c.193A>T
NM_001406645.1:c.193A>T
NM_001406646.1:c.193A>T
NM_001406647.1:c.193A>T
NM_001406648.1:c.193A>T
NM_001406649.1:c.193A>T
NM_001406650.1:c.193A>T
NM_001406651.1:c.193A>T
NM_001406652.1:c.193A>T
NM_001406653.1:c.193A>T
NM_001406654.1:c.-148A>T
NM_001406655.1:c.193A>T
NM_001406656.1:c.-803A>T
NM_001406657.1:c.193A>T
NM_001406658.1:c.-1126A>T
NM_001406659.1:c.-1276A>T
NM_001406660.1:c.-1473A>T
NM_001406661.1:c.-1428A>T
NM_001406662.1:c.-1345A>T
NM_001406666.1:c.193A>T
NM_001406669.1:c.-1276A>T
NM_001406672.1:c.193A>T
NM_001406674.1:c.193A>T
NP_000242.1:p.Lys65Ter
NP_000242.1:p.Lys65Ter
NP_001393560.1:p.Lys65Ter
NP_001393561.1:p.Lys65Ter
NP_001393562.1:p.Lys65Ter
NP_001393563.1:p.Lys65Ter
NP_001393564.1:p.Lys65Ter
NP_001393565.1:p.Lys65Ter
NP_001393566.1:p.Lys65Ter
NP_001393567.1:p.Lys65Ter
NP_001393568.1:p.Lys65Ter
NP_001393569.1:p.Lys65Ter
NP_001393570.1:p.Lys65Ter
NP_001393571.1:p.Lys65Ter
NP_001393572.1:p.Lys65Ter
NP_001393573.1:p.Lys65Ter
NP_001393574.1:p.Lys65Ter
NP_001393575.1:p.Lys65Ter
NP_001393576.1:p.Lys65Ter
NP_001393577.1:p.Lys65Ter
NP_001393578.1:p.Lys65Ter
NP_001393579.1:p.Lys65Ter
NP_001393580.1:p.Lys65Ter
NP_001393581.1:p.Lys65Ter
NP_001393582.1:p.Lys65Ter
NP_001393584.1:p.Lys65Ter
NP_001393586.1:p.Lys65Ter
NP_001393595.1:p.Lys65Ter
NP_001393601.1:p.Lys65Ter
NP_001393603.1:p.Lys65Ter
LRG_218t1:c.193A>T
LRG_218:g.5261A>T
LRG_218p1:p.Lys65Ter
NC_000002.11:g.47630523A>T
NM_000251.1:c.193A>T
NM_000251.2:c.193A>T
NR_176230.1:n.229A>T
NR_176231.1:n.229A>T
NR_176232.1:n.229A>T
NR_176233.1:n.229A>T
NR_176234.1:n.229A>T
NR_176235.1:n.229A>T
NR_176236.1:n.229A>T
NR_176237.1:n.229A>T
NR_176238.1:n.229A>T
NR_176239.1:n.229A>T
NR_176240.1:n.229A>T
NR_176241.1:n.229A>T
NR_176242.1:n.229A>T
NR_176243.1:n.229A>T
NR_176244.1:n.229A>T
NR_176245.1:n.229A>T
NR_176246.1:n.229A>T
NR_176247.1:n.229A>T
NR_176248.1:n.229A>T
NR_176249.1:n.229A>T
NR_176250.1:n.229A>T

Protein change:

K65*

Molecular consequence:

NM_001258281.1:c.-6A>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_000251.3:c.193A>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001406631.1:c.193A>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001406632.1:c.193A>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001406633.1:c.193A>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001406634.1:c.193A>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001406635.1:c.193A>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001406636.1:c.193A>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001406637.1:c.193A>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001406638.1:c.193A>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001406639.1:c.193A>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001406640.1:c.193A>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001406641.1:c.193A>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001406642.1:c.193A>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001406643.1:c.193A>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001406644.1:c.193A>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001406645.1:c.193A>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001406646.1:c.193A>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001406647.1:c.193A>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001406648.1:c.193A>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001406649.1:c.193A>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001406650.1:c.193A>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001406651.1:c.193A>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001406652.1:c.193A>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001406653.1:c.193A>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001406655.1:c.193A>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001406657.1:c.193A>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001406666.1:c.193A>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001406672.1:c.193A>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001406674.1:c.193A>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: MSH2-related disorder
Identifiers:

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004046164	Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004046164

Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego, SCV004046164.1

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

Description

This nonsense variant found in exon 1 of 16 is predicted to result in loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay (NMD). This variant was identified as a somatic alteration in a colorectal tumor (PMID: 30989425). Loss-of-function variation in MSH2 is an established mechanism of disease (PMID: 20301390). The c.193A>T (p.Lys65Ter) variant is absent from the gnomAD population database and thus is presumed to be rare. Based on the available evidence, the c.193A>T (p.Lys65Ter) variant is classified as Likely Pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Nov 10, 2024

ClinVar

Relating variation to medicine