NM_000251.3(MSH2):c.2455A>T (p.Lys819Ter) AND Hereditary cancer-predisposing syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jun 3, 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:: RCV002450538.2

Allele description [Variation Report for NM_000251.3(MSH2):c.2455A>T (p.Lys819Ter)]

NM_000251.3(MSH2):c.2455A>T (p.Lys819Ter)

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.2455A>T (p.Lys819Ter)

HGVS:

NC_000002.12:g.47478516A>T
NG_007110.2:g.80393A>T
NM_000251.3:c.2455A>TMANE SELECT
NM_001258281.1:c.2257A>T
NM_001406631.1:c.2455A>T
NM_001406632.1:c.2455A>T
NM_001406633.1:c.2455A>T
NM_001406634.1:c.2455A>T
NM_001406635.1:c.2455A>T
NM_001406636.1:c.2422A>T
NM_001406637.1:c.2455A>T
NM_001406638.1:c.2494A>T
NM_001406639.1:c.2455A>T
NM_001406640.1:c.2455A>T
NM_001406641.1:c.2455A>T
NM_001406642.1:c.2455A>T
NM_001406643.1:c.2455A>T
NM_001406644.1:c.2455A>T
NM_001406645.1:c.2455A>T
NM_001406646.1:c.2455A>T
NM_001406647.1:c.2305A>T
NM_001406648.1:c.2455A>T
NM_001406649.1:c.2305A>T
NM_001406650.1:c.2305A>T
NM_001406651.1:c.2305A>T
NM_001406652.1:c.2305A>T
NM_001406653.1:c.2395A>T
NM_001406654.1:c.2035A>T
NM_001406656.1:c.1558A>T
NM_001406658.1:c.1099A>T
NM_001406659.1:c.1099A>T
NM_001406660.1:c.1099A>T
NM_001406661.1:c.1099A>T
NM_001406662.1:c.1099A>T
NM_001406669.1:c.1099A>T
NM_001406674.1:c.2455A>T
NP_000242.1:p.Lys819Ter
NP_000242.1:p.Lys819Ter
NP_001245210.1:p.Lys753Ter
NP_001393560.1:p.Lys819Ter
NP_001393561.1:p.Lys819Ter
NP_001393562.1:p.Lys819Ter
NP_001393563.1:p.Lys819Ter
NP_001393564.1:p.Lys819Ter
NP_001393565.1:p.Lys808Ter
NP_001393566.1:p.Lys819Ter
NP_001393567.1:p.Lys832Ter
NP_001393568.1:p.Lys819Ter
NP_001393569.1:p.Lys819Ter
NP_001393570.1:p.Lys819Ter
NP_001393571.1:p.Lys819Ter
NP_001393572.1:p.Lys819Ter
NP_001393573.1:p.Lys819Ter
NP_001393574.1:p.Lys819Ter
NP_001393575.1:p.Lys819Ter
NP_001393576.1:p.Lys769Ter
NP_001393577.1:p.Lys819Ter
NP_001393578.1:p.Lys769Ter
NP_001393579.1:p.Lys769Ter
NP_001393580.1:p.Lys769Ter
NP_001393581.1:p.Lys769Ter
NP_001393582.1:p.Lys799Ter
NP_001393583.1:p.Lys679Ter
NP_001393585.1:p.Lys520Ter
NP_001393587.1:p.Lys367Ter
NP_001393588.1:p.Lys367Ter
NP_001393589.1:p.Lys367Ter
NP_001393590.1:p.Lys367Ter
NP_001393591.1:p.Lys367Ter
NP_001393598.1:p.Lys367Ter
NP_001393603.1:p.Lys819Ter
LRG_218t1:c.2455A>T
LRG_218:g.80393A>T
LRG_218p1:p.Lys819Ter
NC_000002.11:g.47705655A>T
NM_000251.1:c.2455A>T
NM_000251.2:c.2455A>T
NR_176230.1:n.2491A>T
NR_176231.1:n.2459A>T
NR_176232.1:n.2491A>T
NR_176233.1:n.2333A>T
NR_176234.1:n.2491A>T
NR_176235.1:n.2491A>T
NR_176236.1:n.2491A>T
NR_176237.1:n.2491A>T
NR_176238.1:n.2624A>T
NR_176239.1:n.2491A>T
NR_176240.1:n.2286A>T
NR_176241.1:n.2491A>T
NR_176242.1:n.2491A>T
NR_176243.1:n.2341A>T
NR_176244.1:n.2491A>T
NR_176245.1:n.2491A>T
NR_176246.1:n.2491A>T
NR_176247.1:n.2491A>T
NR_176248.1:n.2491A>T
NR_176249.1:n.2721A>T
NR_176250.1:n.2231A>T

Protein change:

K367*

Molecular consequence:

NM_000251.3:c.2455A>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001258281.1:c.2257A>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001406631.1:c.2455A>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001406632.1:c.2455A>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001406633.1:c.2455A>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001406634.1:c.2455A>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001406635.1:c.2455A>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001406636.1:c.2422A>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001406637.1:c.2455A>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001406638.1:c.2494A>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001406639.1:c.2455A>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001406640.1:c.2455A>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001406641.1:c.2455A>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001406642.1:c.2455A>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001406643.1:c.2455A>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001406644.1:c.2455A>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001406645.1:c.2455A>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001406646.1:c.2455A>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001406647.1:c.2305A>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001406648.1:c.2455A>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001406649.1:c.2305A>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001406650.1:c.2305A>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001406651.1:c.2305A>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001406652.1:c.2305A>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001406653.1:c.2395A>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001406654.1:c.2035A>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001406656.1:c.1558A>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001406658.1:c.1099A>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001406659.1:c.1099A>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001406660.1:c.1099A>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001406661.1:c.1099A>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001406662.1:c.1099A>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001406669.1:c.1099A>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001406674.1:c.2455A>T - nonsense - [Sequence Ontology: SO:0001587]

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
SCV002732791	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Jun 3, 2021)	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

SCV002732791

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Jun 3, 2021)

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

Importance of gastric cancer for the diagnosis and surveillance of Japanese Lynch syndrome patients.

Ikenoue T, Arai M, Ishioka C, Iwama T, Kaneko S, Matsubara N, Moriya Y, Nomizu T, Sugano K, Tamura K, Tomita N, Yoshida T, Sugihara K, Naruse H, Yamaguchi K, Nojima M, Nakamura Y, Furukawa Y; Japanese society for cancer of the colon and rectum (JSCCR)..

J Hum Genet. 2019 Dec;64(12):1187-1194. doi: 10.1038/s10038-019-0674-5. Epub 2019 Oct 7. Erratum in: J Hum Genet. 2020 Jul;65(7):633. doi: 10.1038/s10038-020-0747-5.

PubMed [citation]

PMID:: 31588121

Details of each submission

From Ambry Genetics, SCV002732791.2

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

Description

The p.K819* pathogenic mutation (also known as c.2455A>T), located in coding exon 14 of the MSH2 gene, results from an A to T substitution at nucleotide position 2455. This changes the amino acid from a lysine to a stop codon within coding exon 14. This alteration was identified in a Japanese individual diagnosed with colorectal cancer meeting Amsterdam II criteria (Ikenoue T et al. J Hum Genet, 2019 Dec;64:1187-1194). 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: May 1, 2024

ClinVar

Relating variation to medicine