NM_000179.2(MSH6):c.742delC (p.Arg248Glufs) AND Lynch syndrome

Clinical significance:Pathogenic (Last evaluated: Jul 9, 2016)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000477160.1

Allele description

NM_000179.2(MSH6):c.742delC (p.Arg248Glufs)

Gene:
MSH6:mutS homolog 6 [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
2p16.3
Genomic location:
Preferred name:
NM_000179.2(MSH6):c.742delC (p.Arg248Glufs)
HGVS:
  • NC_000002.12:g.47798725delC
  • NG_007111.1:g.20579delC
  • NM_000179.2:c.742delC
  • NM_001281493.1:c.-165delC
  • NP_000170.1:p.Arg248Glufs
  • LRG_219t1:c.742delC
  • LRG_219:g.20579delC
  • LRG_219p1:p.Arg248Glufs
  • NC_000002.11:g.48025864delC
  • p.R248Efs*31
Links:
dbSNP: rs587781691
NCBI 1000 Genomes Browser:
rs587781691
Allele Frequency:
0.00001(-)
Molecular consequence:
  • NM_001281493.1:c.-165delC - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_000179.2:c.742delC - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:
Lynch syndrome (HNPCC)
Synonyms:
Hereditary nonpolyposis colon cancer
Identifiers:
MedGen: C1333990; OMIM: PS120435

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000551199Invitaecriteria provided, single submitter
Pathogenic
(Jul 9, 2016)
germlineclinical testing

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

Summary from all submissions

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

Citations

PubMed

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.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV000551199.2

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

Description

This sequence change deletes 1 nucleotide from exon 4 of the MSH6 mRNA (c.742delC), causing a frameshift at codon 248. This creates a premature translational stop signal (p.Arg248Glufs*31) and is expected to result in an absent or disrupted protein product. While this particular variant has not been reported in the literature, truncating variants in MSH6 are known to be pathogenic (PMID: 24362816, 18269114). ClinVar contains an entry for this variant (Variation ID: 141365). For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: Sep 30, 2018