NM_000179.3(MSH6):c.3850dup (p.Thr1284fs) AND Carcinoma of colon

Clinical significance:Pathogenic

Review status:(0/4) 0 stars out of maximum of 4 stars

no assertion criteria provided

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001353784.1

Allele description [Variation Report for NM_000179.3(MSH6):c.3850dup (p.Thr1284fs)]

NM_000179.3(MSH6):c.3850dup (p.Thr1284fs)

Gene:
MSH6:mutS homolog 6 [Gene - OMIM - HGNC]
Variant type:
Duplication
Cytogenetic location:
2p16.3
Genomic location:
Preferred name:
NM_000179.3(MSH6):c.3850dup (p.Thr1284fs)
HGVS:
  • NC_000002.12:g.47806500dup
  • NG_007111.1:g.28354dup
  • NG_008397.1:g.104176dup
  • NM_000179.2:c.3850dup
  • NM_000179.3:c.3850dupMANE SELECT
  • NM_001281492.2:c.3460dup
  • NM_001281493.2:c.2944dup
  • NM_001281494.2:c.2944dup
  • NP_000170.1:p.Thr1284fs
  • NP_000170.1:p.Thr1284fs
  • NP_001268421.1:p.Thr1154fs
  • NP_001268422.1:p.Thr982fs
  • NP_001268423.1:p.Thr982fs
  • LRG_219t1:c.3850dup
  • LRG_219:g.28354dup
  • LRG_219p1:p.Thr1284fs
  • NC_000002.11:g.48033638_48033639insA
  • NC_000002.11:g.48033639dup
  • NM_000179.2:c.3850dupA
Protein change:
T1154fs
Links:
dbSNP: rs1553333421
NCBI 1000 Genomes Browser:
rs1553333421
Molecular consequence:
  • NM_000179.3:c.3850dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001281492.2:c.3460dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001281493.2:c.2944dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001281494.2:c.2944dup - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:
Carcinoma of colon (CRC)
Synonyms:
Colonic carcinoma; Colorectal cancer, somatic; Rectal cancer, somatic; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0002032; MedGen: C0699790

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000592657Department of Pathology and Laboratory Medicine,Sinai Health System - The Canadian Open Genetics Repository (COGR)

See additional submitters

no assertion criteria providedPathogenicunknownclinical testing

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedunknownyesnot providednot providednot providednot providednot providedclinical testing

Details of each submission

From Department of Pathology and Laboratory Medicine,Sinai Health System - The Canadian Open Genetics Repository (COGR), SCV000592657.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The MSH6 p.Thr1284AsnfsX5 variant was not identified in the literature nor was it identified in the dbSNP, Clinvitae, COSMIC, Mismatch Repair Genes Variant, MMR Gene Unclassified Variants, InSiGHT Colon Cancer Gene Variant (LOVD), Zhejiang Colon Cancer (LOVD), ClinVar, GeneInsight - COGR and UMD databases. The variant was also not identified in the 1000 Genomes Project, NHLBI GO Exome Sequencing Project and the Exome Aggregation Consortium database (August 8, 2016). The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict a difference in splicing. The c.3850dup variant is predicted to cause a frameshift, which alters the protein's amino acid sequence beginning at codon 1284 and leads to a premature stop codon 5 codons downstream. This alteration is then predicted to result in a truncated or absent protein and loss of function. Loss of function variants of the MSH6 gene are an established mechanism of disease in Lynch syndrome and this is the type of variant expected to cause the disorder. In summary, based on the above information, this variant meets our laboratory’s criteria to be classified as pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownyesnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Nov 27, 2021

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