NM_000179.3(MSH6):c.2045_2046del (p.Ser682fs) AND Hereditary cancer-predisposing syndrome

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jul 12, 2016
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:: RCV000491528.1

Allele description

NM_000179.3(MSH6):c.2045_2046del (p.Ser682fs)

Gene:

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

Variant type:

Microsatellite

Cytogenetic location:

2p16.3

Genomic location:

Preferred name:

NM_000179.3(MSH6):c.2045_2046del (p.Ser682fs)

HGVS:

NC_000002.12:g.47800024CT[2]
NG_007111.1:g.21878CT[2]
NM_000179.3:c.2045_2046delMANE SELECT
NM_001281492.2:c.1655_1656del
NM_001281493.2:c.1139_1140del
NM_001281494.2:c.1139_1140del
NP_000170.1:p.Ser682fs
NP_001268421.1:p.Ser552fs
NP_001268422.1:p.Ser380fs
NP_001268423.1:p.Ser380fs
LRG_219:g.21878CT[2]
NC_000002.11:g.48027163CT[2]
NM_000179.2:c.2045_2046delCT

Protein change:

S380fs

Links:

dbSNP: rs267608057

NCBI 1000 Genomes Browser:

rs267608057

Molecular consequence:

NM_000179.3:c.2045_2046del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001281492.2:c.1655_1656del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001281493.2:c.1139_1140del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001281494.2:c.1139_1140del - frameshift variant - [Sequence Ontology: SO:0001589]

Observations:

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000580114	Ambry Genetics	criteria provided, single submitter (Ambry Autosomal Dominant and X-Linked criteria (10/2015))	Pathogenic (Jul 12, 2016)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 18566915, 21836479, 22495361, 29967336 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000580114

Ambry Genetics

criteria provided, single submitter

(Ambry Autosomal Dominant and X-Linked criteria (10/2015))

Pathogenic
(Jul 12, 2016)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	1	not provided	not provided	1	not provided	clinical testing

Citations

PubMed

Major contribution from recurrent alterations and MSH6 mutations in the Danish Lynch syndrome population.

Nilbert M, Wikman FP, Hansen TV, Krarup HB, Orntoft TF, Nielsen FC, Sunde L, Gerdes AM, Cruger D, Timshel S, Bisgaard ML, Bernstein I, Okkels H.

Fam Cancer. 2009;8(1):75-83. doi: 10.1007/s10689-008-9199-3. Epub 2008 Jun 20.

PubMed [citation]

PMID:: 18566915

Challenges in the identification of MSH6-associated colorectal cancer: rectal location, less typical histology, and a subset with retained mismatch repair function.

Klarskov L, Holck S, Bernstein I, Okkels H, Rambech E, Baldetorp B, Nilbert M.

Am J Surg Pathol. 2011 Sep;35(9):1391-9. doi: 10.1097/PAS.0b013e318225c3f0.

PubMed [citation]

PMID:: 21836479

See all PubMed Citations (4)

Details of each submission

From Ambry Genetics, SCV000580114.4

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

Description

The c.2045_2046delCT pathogenic mutation, located in coding exon 4 of the MSH6 gene, results from a deletion of two nucleotides at nucleotide positions 2045 to 2046, causing a translational frameshift with a predicted alternate stop codon (p.S682Cfs*15). <span style="font-family:arial,sans-serif; font-size:10pt">This mutation has been reported in a Danish family with Lynch syndrome (Nilbert M et al. <span style="font-family:arial,sans-serif">Fam. Cancer 2009 Jun;8:75-83; Okkels H et al. Appl. Immunohistochem. Mol. Morphol., 2012 Oct;20:470-7; Klarskov L et al. Am. J. Surg. Pathol., 2011 Sep;35:1391-9). <span style="font-family:arial,sans-serif; font-size:10pt">In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	1	not provided	not provided		1	not provided	not provided	not provided

Last Updated: Nov 5, 2022

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