NM_000179.2(MSH6):c.(?_-1)_457+?del AND Lynch syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: May 28, 2015
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:: RCV000196038.1

Allele description [Variation Report for NM_000179.2(MSH6):c.(?_-1)_457+?del]

NM_000179.2(MSH6):c.(?_-1)_457+?del

Genes:

LOC129933707:ATAC-STARR-seq lymphoblastoid silent region 11468 [Gene]
LOC129933708:ATAC-STARR-seq lymphoblastoid silent region 11469 [Gene]
MSH6:mutS homolog 6 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

2p16.3

Genomic location:

Preferred name:

NM_000179.2(MSH6):c.(?_-1)_457+?del

HGVS:

NC_000002.12:g.(?_47783233)_(47791123_?)del
LRG_219t1:c.(?_-1)_457+?del
NC_000002.11:g.(?_48010372)_(48018262_?)del
NM_000179.2:c.(?_-1)_457+?del

Condition(s)

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

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
SCV000253770	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (May 28, 2015)	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

SCV000253770

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(May 28, 2015)

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	unknown	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

Details of each submission

From Invitae, SCV000253770.2

#	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 exons 1-2 of the MSH6 gene. This deletion extends to both edges of the assayed region, and the 5' and 3' boundaries of this event are not known. However, this deletion removes the initiator methionine in exon 1, and results in the deletion of at least 152 amino acid residues of the MSH6 protein. Gross deletions in MSH6 are known to be pathogenic. Several deletions encompassing exons 1-2 have been reported in the literature in patients affected with Lynch syndrome (PMID: 17117178, 20591884, 22691310, 15942939). For these reasons, this variant has been classified as Pathogenic.

#	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: Oct 14, 2023

ClinVar

Relating variation to medicine