NM_000179.3(MSH6):c.3732_3735dup (p.Ser1246fs) AND Hereditary nonpolyposis colon cancer

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Dec 17, 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:: RCV001192493.1

Allele description [Variation Report for NM_000179.3(MSH6):c.3732_3735dup (p.Ser1246fs)]

NM_000179.3(MSH6):c.3732_3735dup (p.Ser1246fs)

Gene:

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

Variant type:

Duplication

Cytogenetic location:

2p16.3

Genomic location:

Preferred name:

NM_000179.3(MSH6):c.3732_3735dup (p.Ser1246fs)

HGVS:

NC_000002.12:g.47806289_47806292dup
NG_007111.1:g.28143_28146dup
NG_008397.1:g.104386_104389dup
NM_000179.3:c.3732_3735dupMANE SELECT
NM_001281492.2:c.3342_3345dup
NM_001281493.2:c.2826_2829dup
NM_001281494.2:c.2826_2829dup
NP_000170.1:p.Ser1246fs
NP_000170.1:p.Ser1246fs
NP_001268421.1:p.Ser1116fs
NP_001268422.1:p.Ser944fs
NP_001268423.1:p.Ser944fs
LRG_219t1:c.3732_3735dup
LRG_219:g.28143_28146dup
LRG_219p1:p.Ser1246fs
NC_000002.11:g.48033425_48033426insTTAT
NC_000002.11:g.48033428_48033431dup
NM_000179.2:c.3732_3735dup
NM_000179.2:c.3732_3735dupATTT

Protein change:

S1116fs

Links:

dbSNP: rs1553333072

NCBI 1000 Genomes Browser:

rs1553333072

Molecular consequence:

NM_000179.3:c.3732_3735dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001281492.2:c.3342_3345dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001281493.2:c.2826_2829dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001281494.2:c.2826_2829dup - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Hereditary nonpolyposis colon cancer (HNPCC)
Synonyms:: Hereditary nonpolyposis colorectal cancer; Familial nonpolyposis colon cancer; Hereditary Nonpolyposis Colorectal Cancer Syndrome
Identifiers:: MONDO: MONDO:0018630; MedGen: C1333990; OMIM: PS120435

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
SCV001360650	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Likely pathogenic (Dec 17, 2019)	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

SCV001360650

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Likely pathogenic
(Dec 17, 2019)

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

MSH6 and PMS2 germ-line pathogenic variants implicated in Lynch syndrome are associated with breast cancer.

Roberts ME, Jackson SA, Susswein LR, Zeinomar N, Ma X, Marshall ML, Stettner AR, Milewski B, Xu Z, Solomon BD, Terry MB, Hruska KS, Klein RT, Chung WK.

Genet Med. 2018 Oct;20(10):1167-1174. doi: 10.1038/gim.2017.254. Epub 2018 Jan 18.

PubMed [citation]

PMID:: 29345684
PMCID:: PMC6051923

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001360650.1

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

Description

Variant summary: MSH6 c.3732_3735dupATTT (p.Ser1246IlefsX30) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 4e-06 in 251206 control chromosomes (gnomAD). The variant, c.3732_3735dupATTT, has been reported in one unaffected individual who has a family history of cancer (Roberts_2018). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One ClinVar submitter (evaluation after 2014) cites the variant as pathogenic. Based on the evidence outlined above, the variant was classified as likely 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 8, 2024

ClinVar

Relating variation to medicine