NM_000179.3(MSH6):c.1847C>G (p.Ser616Cys) AND Hereditary nonpolyposis colorectal cancer type 5

Clinical significance:Uncertain significance (Last evaluated: May 6, 2021)

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:
RCV000410099.2

Allele description [Variation Report for NM_000179.3(MSH6):c.1847C>G (p.Ser616Cys)]

NM_000179.3(MSH6):c.1847C>G (p.Ser616Cys)

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.1847C>G (p.Ser616Cys)
HGVS:
  • NC_000002.12:g.47799830C>G
  • NG_007111.1:g.21684C>G
  • NM_000179.2:c.1847C>G
  • NM_000179.3:c.1847C>GMANE SELECT
  • NM_001281492.2:c.1457C>G
  • NM_001281493.2:c.941C>G
  • NM_001281494.2:c.941C>G
  • NP_000170.1:p.Ser616Cys
  • NP_000170.1:p.Ser616Cys
  • NP_001268421.1:p.Ser486Cys
  • NP_001268422.1:p.Ser314Cys
  • NP_001268423.1:p.Ser314Cys
  • LRG_219t1:c.1847C>G
  • LRG_219:g.21684C>G
  • LRG_219p1:p.Ser616Cys
  • NC_000002.11:g.48026969C>G
Protein change:
S314C
Links:
dbSNP: rs772363120
NCBI 1000 Genomes Browser:
rs772363120
Molecular consequence:
  • NM_000179.2:c.1847C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_000179.3:c.1847C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001281492.2:c.1457C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001281493.2:c.941C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001281494.2:c.941C>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Hereditary nonpolyposis colorectal cancer type 5 (HNPCC5)
Synonyms:
Hereditary non-polyposis colorectal cancer, type 5
Identifiers:
MONDO: MONDO:0013710; MedGen: C1833477; Orphanet: 144; OMIM: 614350

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000489415Counsylcriteria provided, single submitter
Uncertain significance
(Oct 3, 2016)
unknownclinical testing

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

Counsyl Autosomal Dominant Disease Classification criteria (2015),

Citation Link,

SCV001737487St. Jude Clinical Genomics Lab, St. Jude Children's Research Hospitalcriteria provided, single submitter
Uncertain significance
(May 6, 2021)
germlineclinical testing

Citation Link

Summary from all submissions

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

Citations

PubMed

Improving performance of multigene panels for genomic analysis of cancer predisposition.

Shirts BH, Casadei S, Jacobson AL, Lee MK, Gulsuner S, Bennett RL, Miller M, Hall SA, Hampel H, Hisama FM, Naylor LV, Goetsch C, Leppig K, Tait JF, Scroggins SM, Turner EH, Livingston R, Salipante SJ, King MC, Walsh T, Pritchard CC.

Genet Med. 2016 Oct;18(10):974-81. doi: 10.1038/gim.2015.212. Epub 2016 Feb 4.

PubMed [citation]
PMID:
26845104

Details of each submission

From Counsyl, SCV000489415.1

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

From St. Jude Clinical Genomics Lab, St. Jude Children's Research Hospital, SCV001737487.1

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

Description

The MSH6 c.1847C>G (p.Ser616Cys) missense change has a maximum subpopulation frequency of 0.042% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/variant/2-48026969-C-G?dataset=gnomad_r2_1). Six of seven in silico tools predict a benign effect of this variant on protein function (BP4), but to our knowledge these predictions have not been confirmed by functional assays. This variant has been reported in an individual with a personal history of thyroid, prostate, and kidney cancers (PMID: 26845104). To our knowledge, this variant has not been reported in individuals with Lynch syndrome or CMMRD. In summary, this variant meets criteria to be classified as of uncertain significance based on the ACMG/AMP criteria: BP4.

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

Last Updated: Oct 30, 2021

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