NM_000179.3(MSH6):c.1933_1949del (p.Glu645fs) AND Hereditary nonpolyposis colorectal neoplasms

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 14, 2019
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:: RCV001227347.6

Allele description [Variation Report for NM_000179.3(MSH6):c.1933_1949del (p.Glu645fs)]

NM_000179.3(MSH6):c.1933_1949del (p.Glu645fs)

Gene:

MSH6:mutS homolog 6 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

2p16.3

Genomic location:

Preferred name:

NM_000179.3(MSH6):c.1933_1949del (p.Glu645fs)

HGVS:

NC_000002.12:g.47799916_47799932del
NG_007111.1:g.21770_21786del
NM_000179.3:c.1933_1949delMANE SELECT
NM_001281492.2:c.1543_1559del
NM_001281493.2:c.1027_1043del
NM_001281494.2:c.1027_1043del
NP_000170.1:p.Glu645fs
NP_001268421.1:p.Glu515fs
NP_001268422.1:p.Glu343fs
NP_001268423.1:p.Glu343fs
LRG_219t1:c.1933_1949del
LRG_219:g.21770_21786del
NC_000002.11:g.48027053_48027069del
NC_000002.11:g.48027055_48027071del
NM_000179.2:c.1933_1949del
NM_000179.2:c.1933_1949del17

Protein change:

E343fs

Links:

dbSNP: rs1669395325

NCBI 1000 Genomes Browser:

rs1669395325

Molecular consequence:

NM_000179.3:c.1933_1949del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001281492.2:c.1543_1559del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001281493.2:c.1027_1043del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001281494.2:c.1027_1043del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Hereditary nonpolyposis colorectal neoplasms
Identifiers:: MeSH: D003123; MedGen: C0009405

Recent activity

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Homo sapiens neurexin 2 (NRXN2), transcript variant alpha-2, mRNA
Homo sapiens neurexin 2 (NRXN2), transcript variant alpha-2, mRNA
gi|1677537421|ref|NM_138732.3|

Nucleotide
MYG1 exonuclease isoform X1 [Mus musculus]
MYG1 exonuclease isoform X1 [Mus musculus]
gi|1720384786|ref|XP_030104539.1|

Protein
transmembrane protein 236 isoform X1 [Mus musculus]
transmembrane protein 236 isoform X1 [Mus musculus]
gi|755496843|ref|XP_011237285.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001399700	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 14, 2019)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 18269114, 24362816, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001399700

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 14, 2019)

germline

clinical testing

PubMed (3)
[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

Citations

PubMed

Germline MSH6 mutations are more prevalent in endometrial cancer patient cohorts than hereditary non polyposis colorectal cancer cohorts.

Devlin LA, Graham CA, Price JH, Morrison PJ.

Ulster Med J. 2008 Jan;77(1):25-30.

PubMed [citation]

PMID:: 18269114
PMCID:: PMC2397009

Application of a 5-tiered scheme for standardized classification of 2,360 unique mismatch repair gene variants in the InSiGHT locus-specific database.

Thompson BA, Spurdle AB, Plazzer JP, Greenblatt MS, Akagi K, Al-Mulla F, Bapat B, Bernstein I, Capellá G, den Dunnen JT, du Sart D, Fabre A, Farrell MP, Farrington SM, Frayling IM, Frebourg T, Goldgar DE, Heinen CD, Holinski-Feder E, Kohonen-Corish M, Robinson KL, Leung SY, et al.

Nat Genet. 2014 Feb;46(2):107-115. doi: 10.1038/ng.2854. Epub 2013 Dec 22.

PubMed [citation]

PMID:: 24362816
PMCID:: PMC4294709

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001399700.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in MSH6 are known to be pathogenic (PMID: 18269114, 24362816). This variant has not been reported in the literature in individuals with MSH6-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Glu645Hisfs*10) in the MSH6 gene. It is expected to result in an absent or disrupted protein product.

#	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 8, 2024

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