NM_000251.3(MSH2):c.1983dup (p.Gln662fs) AND Hereditary cancer-predisposing syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Sep 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:: RCV002423717.2

Allele description [Variation Report for NM_000251.3(MSH2):c.1983dup (p.Gln662fs)]

NM_000251.3(MSH2):c.1983dup (p.Gln662fs)

Gene:

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

Variant type:

Duplication

Cytogenetic location:

2p21

Genomic location:

Preferred name:

NM_000251.3(MSH2):c.1983dup (p.Gln662fs)

HGVS:

NC_000002.12:g.47475248dup
NG_007110.2:g.77125dup
NM_000251.3:c.1983dupMANE SELECT
NM_001258281.1:c.1785dup
NM_001406631.1:c.1983dup
NM_001406632.1:c.1983dup
NM_001406633.1:c.1983dup
NM_001406634.1:c.1983dup
NM_001406635.1:c.1983dup
NM_001406636.1:c.1950dup
NM_001406637.1:c.1983dup
NM_001406638.1:c.2022dup
NM_001406639.1:c.1983dup
NM_001406640.1:c.1983dup
NM_001406641.1:c.1983dup
NM_001406642.1:c.1983dup
NM_001406643.1:c.1983dup
NM_001406644.1:c.1983dup
NM_001406645.1:c.1983dup
NM_001406646.1:c.1983dup
NM_001406647.1:c.1833dup
NM_001406648.1:c.1983dup
NM_001406649.1:c.1833dup
NM_001406650.1:c.1833dup
NM_001406651.1:c.1833dup
NM_001406652.1:c.1833dup
NM_001406653.1:c.1923dup
NM_001406654.1:c.1563dup
NM_001406655.1:c.1983dup
NM_001406656.1:c.1086dup
NM_001406657.1:c.*193dup
NM_001406658.1:c.627dup
NM_001406659.1:c.627dup
NM_001406660.1:c.627dup
NM_001406661.1:c.627dup
NM_001406662.1:c.627dup
NM_001406669.1:c.627dup
NM_001406674.1:c.1983dup
NP_000242.1:p.Gln662Thrfs
NP_000242.1:p.Gln662fs
NP_001245210.1:p.Gln596fs
NP_001393560.1:p.Gln662Thrfs
NP_001393561.1:p.Gln662Thrfs
NP_001393562.1:p.Gln662Thrfs
NP_001393563.1:p.Gln662Thrfs
NP_001393564.1:p.Gln662Thrfs
NP_001393565.1:p.Gln651Thrfs
NP_001393566.1:p.Gln662Thrfs
NP_001393567.1:p.Gln675Thrfs
NP_001393568.1:p.Gln662Thrfs
NP_001393569.1:p.Gln662Thrfs
NP_001393570.1:p.Gln662Thrfs
NP_001393571.1:p.Gln662Thrfs
NP_001393572.1:p.Gln662Thrfs
NP_001393573.1:p.Gln662Thrfs
NP_001393574.1:p.Gln662Thrfs
NP_001393575.1:p.Gln662Thrfs
NP_001393576.1:p.Gln612Thrfs
NP_001393577.1:p.Gln662Thrfs
NP_001393578.1:p.Gln612Thrfs
NP_001393579.1:p.Gln612Thrfs
NP_001393580.1:p.Gln612Thrfs
NP_001393581.1:p.Gln612Thrfs
NP_001393582.1:p.Gln642Thrfs
NP_001393583.1:p.Gln522Thrfs
NP_001393584.1:p.Gln662Thrfs
NP_001393585.1:p.Gln363Thrfs
NP_001393587.1:p.Gln210Thrfs
NP_001393588.1:p.Gln210Thrfs
NP_001393589.1:p.Gln210Thrfs
NP_001393590.1:p.Gln210Thrfs
NP_001393591.1:p.Gln210Thrfs
NP_001393598.1:p.Gln210Thrfs
NP_001393603.1:p.Gln662Thrfs
LRG_218t1:c.1983dup
LRG_218:g.77125dup
LRG_218p1:p.Gln662Thrfs
NC_000002.11:g.47702387dup
NM_000251.1:c.1983dupA
NM_000251.2:c.1983dup
NR_176230.1:n.2019dup
NR_176231.1:n.2019dup
NR_176232.1:n.2019dup
NR_176233.1:n.1861dup
NR_176234.1:n.2019dup
NR_176235.1:n.2019dup
NR_176236.1:n.2019dup
NR_176237.1:n.2019dup
NR_176238.1:n.2152dup
NR_176239.1:n.2019dup
NR_176240.1:n.2019dup
NR_176241.1:n.2019dup
NR_176242.1:n.2019dup
NR_176243.1:n.1869dup
NR_176244.1:n.2019dup
NR_176245.1:n.2019dup
NR_176246.1:n.2019dup
NR_176247.1:n.2019dup
NR_176248.1:n.2019dup
NR_176249.1:n.2249dup
NR_176250.1:n.1759dup

Protein change:

Q596fs

Molecular consequence:

NM_000251.3:c.1983dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001258281.1:c.1785dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406631.1:c.1983dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406632.1:c.1983dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406633.1:c.1983dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406634.1:c.1983dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406635.1:c.1983dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406636.1:c.1950dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406637.1:c.1983dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406638.1:c.2022dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406639.1:c.1983dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406640.1:c.1983dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406641.1:c.1983dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406642.1:c.1983dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406643.1:c.1983dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406644.1:c.1983dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406645.1:c.1983dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406646.1:c.1983dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406647.1:c.1833dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406648.1:c.1983dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406649.1:c.1833dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406650.1:c.1833dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406651.1:c.1833dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406652.1:c.1833dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406653.1:c.1923dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406654.1:c.1563dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406655.1:c.1983dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406656.1:c.1086dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406658.1:c.627dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406659.1:c.627dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406660.1:c.627dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406661.1:c.627dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406662.1:c.627dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406669.1:c.627dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406674.1:c.1983dup - 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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002719055	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Sep 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

SCV002719055

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Sep 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

Molecular nature of colon tumors in hereditary nonpolyposis colon cancer, familial polyposis, and sporadic colon cancer.

Konishi M, Kikuchi-Yanoshita R, Tanaka K, Muraoka M, Onda A, Okumura Y, Kishi N, Iwama T, Mori T, Koike M, Ushio K, Chiba M, Nomizu S, Konishi F, Utsunomiya J, Miyaki M.

Gastroenterology. 1996 Aug;111(2):307-17.

PubMed [citation]

PMID:: 8690195

Details of each submission

From Ambry Genetics, SCV002719055.2

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

Description

The c.1983dupA pathogenic mutation, located in coding exon 12 of the MSH2 gene, results from a duplication of A at nucleotide position 1983, causing a translational frameshift with a predicted alternate stop codon (p.Q662Tfs*14). This mutation (designated "661 AAA>AAAA") was identified in the tumor of a patient with HNPCC due to a confirmed germline MSH2 mutation (Konishi M et al. Gastroenterology 1996 Aug;111:307-17). 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: Jun 9, 2024

ClinVar

Relating variation to medicine