NM_000179.3(MSH6):c.1957_1960dup (p.Met654fs) AND Hereditary cancer-predisposing syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: May 27, 2020
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:: RCV001191931.3

Allele description [Variation Report for NM_000179.3(MSH6):c.1957_1960dup (p.Met654fs)]

NM_000179.3(MSH6):c.1957_1960dup (p.Met654fs)

Gene:

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

Variant type:

Duplication

Cytogenetic location:

2p16.3

Genomic location:

Preferred name:

NM_000179.3(MSH6):c.1957_1960dup (p.Met654fs)

HGVS:

NC_000002.12:g.47799940_47799943dup
NG_007111.1:g.21794_21797dup
NM_000179.3:c.1957_1960dupMANE SELECT
NM_001281492.2:c.1567_1570dup
NM_001281493.2:c.1051_1054dup
NM_001281494.2:c.1051_1054dup
NP_000170.1:p.Met654fs
NP_001268421.1:p.Met524fs
NP_001268422.1:p.Met352fs
NP_001268423.1:p.Met352fs
LRG_219:g.21794_21797dup
NC_000002.11:g.48027078_48027079insGTGA
NC_000002.11:g.48027079_48027082dup

Protein change:

M352fs

Links:

dbSNP: rs63751167

NCBI 1000 Genomes Browser:

rs63751167

Molecular consequence:

NM_000179.3:c.1957_1960dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001281492.2:c.1567_1570dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001281493.2:c.1051_1054dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001281494.2:c.1051_1054dup - 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

Mus musculus
Mus musculus
Unraveling the Sox4-orchestrated pro-B cell differentiation program: Intricate roles of the RAG and CK1ε genes (ChIP-Seq)

BioProject
Sulfurovum sp. AR strain:AR
Sulfurovum sp. AR strain:AR
Draft genome sequence of Sulfurovum sp. strain AR

BioProject
iso glutaminyl cyclase, isoform B [Drosophila melanogaster]
iso glutaminyl cyclase, isoform B [Drosophila melanogaster]
gi|28574640|ref|NP_788550.1|

Protein
Homo sapiens sulfide quinone reductase-like (yeast), mRNA (cDNA clone MGC:10012 ...
Homo sapiens sulfide quinone reductase-like (yeast), mRNA (cDNA clone MGC:10012 IMAGE:3884024), complete cds
gi|16877129|gb|BC016836.1|

Nucleotide
htpX [Burkholderia cepacia]
htpX [Burkholderia cepacia]
Gene ID:56663163

Gene

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
SCV001359869	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (May 27, 2020)	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

SCV001359869

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(May 27, 2020)

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

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Color Diagnostics, LLC DBA Color Health, SCV001359869.2

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

Description

This variant inserts 4 nucleotides in exon 4 of the MSH6 gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in an individual affected with colorectal cancer (PMID: 14574004). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of MSH6 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is 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 8, 2024

ClinVar

Relating variation to medicine