NM_000179.3(MSH6):c.2555AGA[2] (p.Lys854del) AND not provided

Clinical significance:Uncertain significance (Last evaluated: May 15, 2018)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000656896.1

Allele description [Variation Report for NM_000179.3(MSH6):c.2555AGA[2] (p.Lys854del)]

NM_000179.3(MSH6):c.2555AGA[2] (p.Lys854del)

Gene:
MSH6:mutS homolog 6 [Gene - OMIM - HGNC]
Variant type:
Microsatellite
Cytogenetic location:
2p16.3
Genomic location:
Preferred name:
NM_000179.3(MSH6):c.2555AGA[2] (p.Lys854del)
HGVS:
  • NC_000002.12:g.47800538AGA[2]
  • NG_007111.1:g.22392AGA[2]
  • NM_000179.3:c.2555AGA[2]MANE SELECT
  • NM_001281492.2:c.2165AGA[2]
  • NM_001281493.2:c.1649AGA[2]
  • NM_001281494.2:c.1649AGA[2]
  • NP_000170.1:p.Lys854del
  • NP_001268421.1:p.Lys724del
  • NP_001268422.1:p.Lys552del
  • NP_001268423.1:p.Lys552del
  • LRG_219:g.22392AGA[2]
  • NC_000002.11:g.48027676_48027678del
  • NC_000002.11:g.48027677AGA[2]
  • NM_000179.2:c.2561_2563delAGA
  • NM_000179.3:c.2561_2563delAGAMANE SELECT
  • p.K854del
Protein change:
K552del
Links:
dbSNP: rs587782858
NCBI 1000 Genomes Browser:
rs587782858
Molecular consequence:
  • NM_000179.3:c.2555AGA[2] - inframe_deletion - [Sequence Ontology: SO:0001822]
  • NM_001281492.2:c.2165AGA[2] - inframe_deletion - [Sequence Ontology: SO:0001822]
  • NM_001281493.2:c.1649AGA[2] - inframe_deletion - [Sequence Ontology: SO:0001822]
  • NM_001281494.2:c.1649AGA[2] - inframe_deletion - [Sequence Ontology: SO:0001822]

Condition(s)

Identifiers:
MedGen: CN517202

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000565226GeneDxcriteria provided, single submitter
Uncertain significance
(Jan 12, 2018)
germlineclinical testing

Citation Link,

SCV000888259Quest Diagnostics Nichols Institute San Juan Capistranocriteria provided, single submitter
Uncertain significance
(May 15, 2018)
germlineclinical testing

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

Summary from all submissions

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

Citations

PubMed

A Standardized DNA Variant Scoring System for Pathogenicity Assessments in Mendelian Disorders.

Karbassi I, Maston GA, Love A, DiVincenzo C, Braastad CD, Elzinga CD, Bright AR, Previte D, Zhang K, Rowland CM, McCarthy M, Lapierre JL, Dubois F, Medeiros KA, Batish SD, Jones J, Liaquat K, Hoffman CA, Jaremko M, Wang Z, Sun W, Buller-Burckle A, et al.

Hum Mutat. 2016 Jan;37(1):127-34. doi: 10.1002/humu.22918. Epub 2015 Oct 29.

PubMed [citation]
PMID:
26467025
PMCID:
PMC4737317

Details of each submission

From GeneDx, SCV000565226.5

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

Description

This deletion of three nucleotides in MSH6 is denoted c.2561_2563delAGA at the cDNA level and p.Lys854del at the protein level. The normal sequence, with the bases that are deleted in brackets, is AAGA[delAGA]TTAT. Although this variant was observed in a case of possible constitutional mismatch repair deficiency (CMMR-D), sequencing and deletion/duplication of all mismatch repair genes were not performed and therefore this variant may not be responsible for the phenotype (Bougeard 2014). This variant was not observed at a significant allele frequency in large population cohorts (Lek 2016). This in-frame deletion of a single Lysine residue is located in the lever domain (Warren 2007, Kansikas 2010). In-silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect. Since in-frame deletions may or may not inhibit proper protein functioning, the clinical significance of this finding remains unclear at this time and we consider MSH6 Lys854del to be a variant of uncertain significance.

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

From Quest Diagnostics Nichols Institute San Juan Capistrano, SCV000888259.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Jun 14, 2021

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