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NM_000179.3(MSH6):c.3477C>A (p.Tyr1159Ter) AND Carcinoma of colon

Germline classification:
Likely pathogenic (1 submission)
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
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:
RCV001354656.9

Allele description [Variation Report for NM_000179.3(MSH6):c.3477C>A (p.Tyr1159Ter)]

NM_000179.3(MSH6):c.3477C>A (p.Tyr1159Ter)

Gene:
MSH6:mutS homolog 6 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
2p16.3
Genomic location:
Preferred name:
NM_000179.3(MSH6):c.3477C>A (p.Tyr1159Ter)
Other names:
NP_000170.1:p.Tyr1159*
HGVS:
  • NC_000002.12:g.47804948C>A
  • NG_007111.1:g.26802C>A
  • NG_008397.1:g.105728G>T
  • NM_000179.3:c.3477C>AMANE SELECT
  • NM_001281492.2:c.3087C>A
  • NM_001281493.2:c.2571C>A
  • NM_001281494.2:c.2571C>A
  • NP_000170.1:p.Tyr1159Ter
  • NP_000170.1:p.Tyr1159Ter
  • NP_001268421.1:p.Tyr1029Ter
  • NP_001268422.1:p.Tyr857Ter
  • NP_001268423.1:p.Tyr857Ter
  • LRG_219t1:c.3477C>A
  • LRG_219:g.26802C>A
  • LRG_219p1:p.Tyr1159Ter
  • NC_000002.11:g.48032087C>A
  • NM_000179.2:c.3477C>A
Protein change:
Y1029*
Links:
dbSNP: rs398123231
NCBI 1000 Genomes Browser:
rs398123231
Molecular consequence:
  • NM_000179.3:c.3477C>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001281492.2:c.3087C>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001281493.2:c.2571C>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001281494.2:c.2571C>A - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:
Carcinoma of colon (CRC)
Synonyms:
Colonic carcinoma; Colon carcinoma
Identifiers:
MONDO: MONDO:0002032; MedGen: C0699790

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001549322Department of Pathology and Laboratory Medicine, Sinai Health System - The Canadian Open Genetics Repository (COGR)

See additional submitters

no assertion criteria provided
Likely pathogenicunknownclinical testing

Help

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), SCV001549322.1

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

Description

The MSH6 p.Tyr1159* variant was identified in 2 of 5260 proband chromosomes (frequency: 0.0004) from individuals or families with colon cancer (Bonadona 2011, Perez-Cabornell 2011). The variant was also identified in dbSNP (ID: rs398123231) as “With Pathogenic, Uncertain significance allele"), ClinVar (classified as pathogenic by Invitae, Ambry Genetics, and two other clinical laboratories), UMD-LSDB (12x as causal), and in Insight InSiGHT Hereditary Tumors databases. The variant was not identified in the COGR, Cosmic, MutDB, Zhejiang University Database, and or Mismatch Repair Genes Variant databases. The variant was not identified in the following control databases: the 1000 Genomes Project, the NHLBI GO Exome Sequencing Project, the Exome Aggregation Consortium (August 8th 2016), or the Genome Aggregation Database (Feb 27, 2017). The p.Tyr1159* variant leads to a premature stop codon at position 1159, which is predicted to lead to 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: Oct 26, 2024