Variant "CCDC28B:c.330C>T(p.Phe110Phe)"
Search results: 2 records
Variant information
Gene:
CCDC28B 
Variant:
CCDC28B:c.330C>T(p.Phe110Phe) 
Genomic location:
chr1:32669645(hg19) 
HGVS:
SO Term RefSeq
protein_coding NM_001301011.1:c.330C>T(p.Phe110Phe)
protein_coding NM_024296.4:c.330C>T(p.Phe110Phe)
protein_coding NM_001160042.1:c.-1638C>T
protein_coding NM_018134.2:c.-1638C>T
Alias:
CCDC28B:rs41263993 
dbSNP ID:
rs41263993  
GWAS trait:
no data 
Modifier statisitcs
Record:
2 
Disorder:
1 
Reference:
2 
Effect type:
Expressivity(2)  
Modifier effect:
Altered effect of disease causing mutation(1) ,Altered severity(1)  
Details：
  • Target disease:
    Bardet-Biedl Syndrome (DOID_1935)
    Effect type:
    Expressivity 
    Modifier effect:
    Altered severity 
    Evidence:
    Assessment of genotype–phenotype associations 
    Effect:
    CCDC28B and TMEM67, have been reported as modifier alleles that in the heterozygous state could increase the severity of BBS caused by a homozygous mutation in another BBS gene.
    Alias in reference:
    CCDC28B:c.330C>T(p.Phe110Phe)
    Reference:
    PMID29127258
    Title:
    Homozygous mutation in CEP19, a gene mutated in morbid obesity, in Bardet-Biedl syndrome with predominant postaxial polydactyly.
    Species studied:
    Human
    Abstract:
    Bardet-Biedl syndrome (BBS) is a ciliopathy with extensive phenotypic variability and genetic heterogeneity. We aimed to discover the gene mutated in a consanguineous kindred with multiple cases of a BBS phenotype.
  • Target disease:
    Bardet-Biedl Syndrome (DOID_1935)
    Effect type:
    Expressivity 
    Modifier effect:
    Altered effect of disease causing mutation 
    Evidence:
    Gene activity study 
    Effect:
    epistatic allele
    Alias in reference:
    CCDC28B:rs41263993
    Reference:
    PMID16327777
    Title:
    Dissection of epistasis in oligogenic Bardet-Biedl syndrome.
    Species studied:
    Human
    Abstract:
    Epistatic interactions have an important role in phenotypic variability, yet the genetic dissection of such phenomena remains challenging. Here we report the identification of a novel locus, MGC1203, that contributes epistatic alleles to Bardet-Biedl syndrome (BBS), a pleiotropic, oligogenic disorder. MGC1203 encodes a pericentriolar protein that interacts and colocalizes with the BBS proteins. Sequencing of two independent BBS cohorts revealed a significant enrichment of a heterozygous C430T mutation in patients, and a transmission disequilibrium test (TDT) showed strong over-transmission of this variant. Further analyses showed that the 430T allele enhances the use of a cryptic splice acceptor site, causing the introduction of a premature termination codon (PTC) and the reduction of steady-state MGC1203 messenger RNA levels. Finally, recapitulation of the human genotypes in zebrafish shows that modest suppression of mgc1203 exerts an epistatic effect on the developmental phenotype of BBS morphants. Our data demonstrate how the combined use of biochemical, genetic and in vivo tools can facilitate the dissection of epistatic phenomena, and enhance our appreciation of the genetic basis of phenotypic variability.