NC_000002.12:g.(?_47482779)_(47482949_?)del AND Lynch syndrome

This record was updated by the submitter. Please see the current version.

Germline classification:: Conflicting classifications of pathogenicity (2 submissions)
Last evaluated:: Dec 19, 2016
Review status:: criteria provided, conflicting classifications

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:: RCV000501558.3

Allele description

NC_000002.12:g.(?_47482779)_(47482949_?)del

Gene:

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

Variant type:

Deletion

Cytogenetic location:

2p21

Genomic location:

Preferred name:

NC_000002.12:g.(?_47482779)_(47482949_?)del

HGVS:

NC_000002.12:g.(?_47482779)_(47482949_?)del
NC_000002.11:g.(?_47709918)_(47710088_?)del
NM_000251.2:c.2635-?_2805+?del

Condition(s)

Name:: Lynch syndrome
Identifiers:: MONDO: MONDO:0005835; MedGen: C4552100

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000254414	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Dec 19, 2016)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV000591000	Department of Pathology and Laboratory Medicine, Sinai Health System - The Canadian Open Genetics Repository (COGR)	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Aug 14, 2014)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 24323032, 24278394, 15942939, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000254414

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Dec 19, 2016)

germline

clinical testing

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

SCV000591000

Department of Pathology and Laboratory Medicine, Sinai Health System - The Canadian Open Genetics Repository (COGR)

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Aug 14, 2014)

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
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240-242.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Tumor mismatch repair immunohistochemistry and DNA MLH1 methylation testing of patients with endometrial cancer diagnosed at age younger than 60 years optimizes triage for population-level germline mismatch repair gene mutation testing.

Buchanan DD, Tan YY, Walsh MD, Clendenning M, Metcalf AM, Ferguson K, Arnold ST, Thompson BA, Lose FA, Parsons MT, Walters RJ, Pearson SA, Cummings M, Oehler MK, Blomfield PB, Quinn MA, Kirk JA, Stewart CJ, Obermair A, Young JP, Webb PM, Spurdle AB.

J Clin Oncol. 2014 Jan 10;32(2):90-100. doi: 10.1200/JCO.2013.51.2129. Epub 2013 Dec 9.

PubMed [citation]

PMID:: 24323032
PMCID:: PMC4876359

See all PubMed Citations (5)

Details of each submission

From Invitae, SCV000254414.3

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

Description

This sequence change is a gross deletion of the genomic region encompassing exon 16 of the MSH2 gene. It is expected to result in the loss of the terminal 56 amino acids of the MSH2 protein. This deletion has been reported in the literature in individuals affected with Lynch syndrome and endometrial cancer (PMID: 24278394, 15942939, 18931482, 24323032). Segregation studies have not been reported for this variant. This variant is also known as c.2635+?_(*3084)del, and c.2635-?_( 272_?)del in the literature. In summary, this variant leads to loss of the last exon of the MSH2 gene. This deletion has been reported in affected patients, but it is not known whether it affects MSH2 protein function or segregates with disease. For these reasons, this change has been classified as a Variant of Uncertain Significance.

#	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

From Department of Pathology and Laboratory Medicine, Sinai Health System - The Canadian Open Genetics Repository (COGR), SCV000591000.1

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

#	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: Mar 26, 2023

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