NM_005902.4(SMAD3):c.802C>T (p.Arg268Cys) AND not provided

Clinical significance:Pathogenic/Likely pathogenic (Last evaluated: May 19, 2021)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
4 submissions [Details]
Record status:
current
Accession:
RCV000179456.7

Allele description [Variation Report for NM_005902.4(SMAD3):c.802C>T (p.Arg268Cys)]

NM_005902.4(SMAD3):c.802C>T (p.Arg268Cys)

Gene:
SMAD3:SMAD family member 3 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
15q22.33
Genomic location:
Preferred name:
NM_005902.4(SMAD3):c.802C>T (p.Arg268Cys)
Other names:
p.R268C:CGC>TGC
HGVS:
  • NC_000015.10:g.67181384C>T
  • NG_011990.1:g.120528C>T
  • NM_001145102.1:c.487C>T
  • NM_001145103.1:c.670C>T
  • NM_001145104.1:c.217C>T
  • NM_005902.4:c.802C>TMANE SELECT
  • NP_001138574.1:p.Arg163Cys
  • NP_001138575.1:p.Arg224Cys
  • NP_001138576.1:p.Arg73Cys
  • NP_005893.1:p.Arg268Cys
  • NC_000015.9:g.67473722C>T
  • NM_005902.3:c.802C>T
Protein change:
R163C
Links:
dbSNP: rs794727798
NCBI 1000 Genomes Browser:
rs794727798
Molecular consequence:
  • NM_001145102.1:c.487C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001145103.1:c.670C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001145104.1:c.217C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_005902.4:c.802C>T - missense variant - [Sequence Ontology: SO:0001583]
Observations:
3

Condition(s)

Identifiers:
MedGen: CN517202

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000231708EGL Genetic Diagnostics, Eurofins Clinical Diagnosticscriteria provided, single submitter
Pathogenic
(Oct 27, 2015)
germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Citation Link,

SCV000250758GeneDxcriteria provided, single submitter
Likely pathogenic
(May 19, 2021)
germlineclinical testing

Citation Link,

SCV001808492Genome Diagnostics Laboratory, Amsterdam University Medical Center - VKGL Data-share Consensusno assertion criteria providedLikely pathogenicgermlineclinical testing

SCV001964192Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center - VKGL Data-share Consensus

See additional submitters

no assertion criteria providedLikely pathogenicgermlineclinical testing

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing
not providedgermlineunknown3not providednot providednot providednot providedclinical testing

Citations

PubMed

Mutations in protein-binding hot-spots on the hub protein Smad3 differentially affect its protein interactions and Smad3-regulated gene expression.

Schiro MM, Stauber SE, Peterson TL, Krueger C, Darnell SJ, Satyshur KA, Drinkwater NR, Newton MA, Hoffmann FM.

PLoS One. 2011;6(9):e25021. doi: 10.1371/journal.pone.0025021. Epub 2011 Sep 19.

PubMed [citation]
PMID:
21949838
PMCID:
PMC3176292
See all PubMed Citations (4)

Details of each submission

From EGL Genetic Diagnostics, Eurofins Clinical Diagnostics, SCV000231708.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided3not providednot providedclinical testing PubMed (4)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot provided3not providednot providednot provided

From GeneDx, SCV000250758.12

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

Description

Not observed in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Published in vitro functional studies suggest decreased transcriptional activity; however, it is unknown whether these findings replicate in vivo effect (Stroschein et al., 1999; Fleming et al., 2013); Reported in ClinVar (ClinVar Variant ID# 198187; Landrum et al., 2016); This variant is associated with the following publications: (PMID: 32123317, 29907982, 21949838, 25944730, 23139211, 10092624)

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

From Genome Diagnostics Laboratory, Amsterdam University Medical Center - VKGL Data-share Consensus, SCV001808492.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

From Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center - VKGL Data-share Consensus, SCV001964192.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Oct 6, 2021

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