Skeletal ciliopathies

Gene: C21orf2

Green List (high evidence)

C21orf2 (chromosome 21 open reading frame 2)
EnsemblGeneIds (GRCh38): ENSG00000160226
EnsemblGeneIds (GRCh37): ENSG00000160226
OMIM: 603191, Gene2Phenotype
C21orf2 is in 10 panels

3 reviews

Rebecca Foulger (Genomics England curator)

Comment on list classification: Updated rating from Grey to Green: Two Green expert reviews, plus recent literature evidence for biallelic C21orf2 variants involved in Jeune syndrome (PMID:26167768).
Created: 16 Oct 2018, 2:46 p.m.
Comment on mode of inheritance: Biallelic MOI confirmed by OMIM and DD-G2P.
Created: 16 Oct 2018, 2:29 p.m.
Added new-gene-name tag: new approved HGNC gene symbol is CFAP410.
Created: 16 Oct 2018, 2:25 p.m.

Andrea Nemeth (University of Oxford)

Green List (high evidence)

C21ORF2 first reported as a cause of autosomal recessive cone-rod dystrophy (a homozygous
splicing mutation), but it was a single family (23105016). This gene was then identified as a cilial gene in a Nature Genetics paper (26167768), using a genome-wide siRNA knockdown strategy for ciliogenesis. Included within this paper were four families, all of whom had homozygous or compound heterozygous mutations and a spectrum of clinical phenotypes including retinal dystrophy with additional thoracic outlet features in some. Most recently another paper has described axial SMD in cases with mutations in this gene.
Created: 16 Sep 2018, 7:08 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Axial Spondylometaphyseal Dysplasia (axial SMD); Jeune Syndrome; Retinal Dystrophy


Zornitza Stark (Australian Genomics)

Green List (high evidence)

Multiple affected individuals from unrelated families reported with bi-allelic variants in this gene, associated with a skeletal/retinal phenotype consistent with a ciliopathy.
Created: 3 Aug 2018, 6:47 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Spondylometaphyseal dysplasia, axial, MIM#602271


Variants in this GENE are reported as part of current diagnostic practice


Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
  • Expert Review Green
  • Expert list
  • Expert Review Green
  • Jeune asphyxiating thoracic dystrophy (JATD)
  • Jeune Syndrome
  • Spondylometaphyseal dysplasia, axial, 602271
  • Retinal dystrophy with macular staphyloma, 617547
Clinvar variants
Variants in C21orf2
Panels with this gene

History Filter Activity

18 Dec 2019, Gel status: 3

Added Tag

Louise Daugherty (Genomics England Curator)

Tag new-gene-name tag was added to gene: C21orf2.

10 Jul 2019, Gel status: 3

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes

Eleanor Williams (Genomics England Curator)

gene: C21orf2 was added gene: C21orf2 was added to Skeletal ciliopathies. Sources: Expert list,Expert Review Green Mode of inheritance for gene: C21orf2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: C21orf2 were set to 26974433; 27548899; 23105016; 26167768 Phenotypes for gene: C21orf2 were set to Jeune asphyxiating thoracic dystrophy (JATD); Jeune Syndrome; Spondylometaphyseal dysplasia, axial, 602271; Retinal dystrophy with macular staphyloma, 617547