NM_000179.2(MSH6):c.2561_2562delinsTT (p.Lys854Ile) AND not specified

Clinical significance:Uncertain significance (Last evaluated: May 17, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001193127.1

Allele description [Variation Report for NM_000179.2(MSH6):c.2561_2562delinsTT (p.Lys854Ile)]

NM_000179.2(MSH6):c.2561_2562delinsTT (p.Lys854Ile)

Gene:
MSH6:mutS homolog 6 [Gene - OMIM - HGNC]
Variant type:
Indel
Cytogenetic location:
2p16.3
Genomic location:
Preferred name:
NM_000179.2(MSH6):c.2561_2562delinsTT (p.Lys854Ile)
HGVS:
  • NC_000002.12:g.47800544_47800545delinsTT
  • NG_007111.1:g.22398_22399delinsTT
  • NM_000179.2:c.2561_2562delinsTT
  • NM_001281492.1:c.2171_2172delinsTT
  • NM_001281493.1:c.1655_1656delinsTT
  • NM_001281494.1:c.1655_1656delinsTT
  • NP_000170.1:p.Lys854Ile
  • NP_001268421.1:p.Lys724Ile
  • NP_001268422.1:p.Lys552Ile
  • NP_001268423.1:p.Lys552Ile
  • LRG_219t1:c.2561_2562delinsTT
  • LRG_219:g.22398_22399delinsTT
  • LRG_219p1:p.Lys854Ile
  • NC_000002.11:g.48027683_48027684delAGinsTT
  • NC_000002.11:g.48027683_48027684delinsTT
  • NM_000179.2:c.2561_2562delAGinsTT
Protein change:
K552I
Links:
dbSNP: rs587780673
NCBI 1000 Genomes Browser:
rs587780673
Molecular consequence:
  • NM_000179.2:c.2561_2562delinsTT - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001281492.1:c.2171_2172delinsTT - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001281493.1:c.1655_1656delinsTT - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001281494.1:c.1655_1656delinsTT - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001361764Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
Uncertain significance
(May 17, 2019)
germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Citation Link

Summary from all submissions

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

Citations

PubMed

Assigning clinical meaning to somatic and germ-line whole-exome sequencing data in a prospective cancer precision medicine study.

Ghazani AA, Oliver NM, St Pierre JP, Garofalo A, Rainville IR, Hiller E, Treacy DJ, Rojas-Rudilla V, Wood S, Bair E, Parello M, Huang F, Giannakis M, Wilson FH, Stover EH, Corsello SM, Nguyen T, Rana HQ, Church AJ, Lowenstein C, Cibulskis C, Amin-Mansour A, et al.

Genet Med. 2017 Jul;19(7):787-795. doi: 10.1038/gim.2016.191. Epub 2017 Jan 26.

PubMed [citation]
PMID:
28125075

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001361764.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

Variant summary: MSH6 c.2561_2562delinsTT (p.Lys854Ile) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 3.6e-06 in 280654 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. The variant, c.2561_2562delinsTT, has been reported in the literature in individuals affected with breast cancer or colon cancer (Zick_2015, Ghazani_2017). These reports do not provide unequivocal conclusions about association of the variant with Lynch Syndrome. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation (VUS (n=2), Likely benign (n=1)). Based on the evidence outlined above, the variant was classified as uncertain significance.

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

Last Updated: Aug 11, 2021

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