NM_000179.3(MSH6):c.723dup (p.Ser242Ter) AND Hereditary nonpolyposis colorectal neoplasms

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Mar 8, 2023
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:: RCV000701122.7

Allele description [Variation Report for NM_000179.3(MSH6):c.723dup (p.Ser242Ter)]

NM_000179.3(MSH6):c.723dup (p.Ser242Ter)

Gene:

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

Variant type:

Duplication

Cytogenetic location:

2p16.3

Genomic location:

Preferred name:

NM_000179.3(MSH6):c.723dup (p.Ser242Ter)

HGVS:

NC_000002.12:g.47798706dup
NG_007111.1:g.20560dup
NM_000179.3:c.723dupMANE SELECT
NM_001281492.2:c.333dup
NM_001281493.2:c.-184dup
NM_001281494.2:c.-184dup
NP_000170.1:p.Ser242Ter
NP_001268421.1:p.Ser112Ter
LRG_219:g.20560dup
NC_000002.11:g.48025844_48025845insT
NC_000002.11:g.48025845dup
NM_000179.2:c.723dupT

Protein change:

S112*

Links:

dbSNP: rs1558659056

NCBI 1000 Genomes Browser:

rs1558659056

Molecular consequence:

NM_001281493.2:c.-184dup - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001281494.2:c.-184dup - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_000179.3:c.723dup - nonsense - [Sequence Ontology: SO:0001587]
NM_001281492.2:c.333dup - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000829905	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Mar 8, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 20487569, 18269114, 24362816, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000829905

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Mar 8, 2023)

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

Citations

PubMed

MSH6 and PMS2 mutation positive Australian Lynch syndrome families: novel mutations, cancer risk and age of diagnosis of colorectal cancer.

Talseth-Palmer BA, McPhillips M, Groombridge C, Spigelman A, Scott RJ.

Hered Cancer Clin Pract. 2010 May 21;8(1):5. doi: 10.1186/1897-4287-8-5.

PubMed [citation]

PMID:: 20487569
PMCID:: PMC2890527

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

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000829905.4

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

Description

For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 578189). This premature translational stop signal has been observed in individual(s) with Lynch syndrome (PMID: 20487569). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ser242*) in the MSH6 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MSH6 are known to be pathogenic (PMID: 18269114, 24362816).

#	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: Sep 29, 2024

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