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NM_000179.2(MSH6):c.2561_2563delAGA (p.Lys854del) AND Hereditary nonpolyposis colon cancer

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Nov 26, 2017
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:
RCV000226221.4

Allele description

NM_000179.2(MSH6):c.2561_2563delAGA (p.Lys854del)

Gene:
MSH6:mutS homolog 6 [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
2p16.3
Genomic location:
Preferred name:
NM_000179.2(MSH6):c.2561_2563delAGA (p.Lys854del)
HGVS:
  • NC_000002.12:g.47800544_47800546delAGA
  • NG_007111.1:g.22398_22400delAGA
  • NM_000179.2:c.2561_2563delAGA
  • NP_000170.1:p.Lys854del
  • LRG_219t1:c.2561_2563delAGA
  • LRG_219:g.22398_22400delAGA
  • LRG_219p1:p.Lys854del
  • NC_000002.11:g.48027683_48027685delAGA
  • p.K854del
Protein change:
K854del
Links:
dbSNP: rs587782858
NCBI 1000 Genomes Browser:
rs587782858
Molecular consequence:
  • NM_000179.2:c.2561_2563delAGA - inframe_variant - [Sequence Ontology: SO:0001650]

Condition(s)

Name:
Hereditary nonpolyposis colon cancer
Identifiers:
MedGen: C0009405; Orphanet: 443090

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000283756Invitae
criteria provided, single submitter

(Nykamp K et al. (Genet Med 2017))
Uncertain significance
(Nov 26, 2017)
germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Summary from all submissions

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

Citations

PubMed

Constitutional mismatch repair deficiency syndrome: clinical description in a French cohort.

Lavoine N, Colas C, Muleris M, Bodo S, Duval A, Entz-Werle N, Coulet F, Cabaret O, Andreiuolo F, Charpy C, Sebille G, Wang Q, Lejeune S, Buisine MP, Leroux D, Couillault G, Leverger G, Fricker JP, Guimbaud R, Mathieu-Dramard M, Jedraszak G, Cohen-Hagenauer O, et al.

J Med Genet. 2015 Nov;52(11):770-8. doi: 10.1136/jmedgenet-2015-103299. Epub 2015 Aug 28. Review.

PubMed [citation]
PMID:
26318770

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV000283756.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

This sequence change deletes 3 nucleotides from exon 4 of the MSH6 mRNA (c.2561_2563delAGA). This leads to the deletion of 1 amino acid residue in the MSH6 protein (p.Lys854del) but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs751683437, ExAC 0.003%). This variant has been observed on the opposite chromosome (in trans) from a pathogenic variant in an individual affected with constitutional mismatch repair deficiency syndrome (PMID: 26318770). This finding is consistent with autosomal recessive inheritance, and suggests that this variant contributes to disease. ClinVar contains an entry for this variant (Variation ID: 142970). Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the deleted amino acid is currently unknown. In summary, this is a rare in-frame deletion of 1 amino acid residue with uncertain impact on protein function. It has been reported in the population and an affected individual, but the available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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

Last Updated: Jul 21, 2018