GeneBe

DCDC2

doublecortin domain containing 2, the group of Doublecortin superfamily

Basic information

Region (hg38): 6:24171755-24358059

Previous symbols: [ "DFNB66" ]

Links

ENSG00000146038 ∙ NCBI:51473 ∙ OMIM:605755 ∙ HGNC:18141 ∙ Uniprot:Q9UHG0 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

  • autosomal recessive nonsyndromic hearing loss 66 (Limited), mode of inheritance: AR
  • nephronophthisis 19 (Strong), mode of inheritance: AR
  • nephronophthisis 19 (Strong), mode of inheritance: AR
  • autosomal recessive nonsyndromic hearing loss 66 (Limited), mode of inheritance: AR
  • Senior-Boichis syndrome (Supportive), mode of inheritance: AR
  • hearing loss, autosomal recessive (Supportive), mode of inheritance: AR
  • isolated neonatal sclerosing cholangitis (Supportive), mode of inheritance: AR
  • autosomal recessive nonsyndromic hearing loss 66 (Limited), mode of inheritance: Unknown
  • isolated neonatal sclerosing cholangitis (Strong), mode of inheritance: AR
  • nephronophthisis 19 (Strong), mode of inheritance: AR
  • ciliopathy (Definitive), mode of inheritance: AR
  • ciliopathy (Definitive), mode of inheritance: AR
  • nonsyndromic genetic hearing loss (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Deafness, autosomal recessive 66; Nephronophthisis 19; Sclerosing cholangitis, neonatalARAudiologic/Otolaryngologic; GastrointestinalEarly recognition and treatment of hearing impairment may improve outcomes, including speech and language development; In Nephronophthisis 19 and Sclerosing cholangitis, individuals may present with hepatic dysfunction, and awareness may allow early diagnosis and managementAudiologic/Otolaryngologic; Gastrointestinal; Renal16244493; 25557784; 25601850; 27319779; 27469900
In Nephronophthisis 19 and Sclerosing cholangitis, liver transplant has been described

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DCDC2 gene.

  • Isolated_neonatal_sclerosing_cholangitis (207 variants)
  • Autosomal_recessive_nonsyndromic_hearing_loss_66 (201 variants)
  • not_provided (109 variants)
  • Nephronophthisis_19 (88 variants)
  • Inborn_genetic_diseases (54 variants)
  • DCDC2-related_disorder (49 variants)
  • not_specified (15 variants)
  • Nonsyndromic_Deafness (1 variants)
  • Neonatal_ichthyosis-sclerosing_cholangitis_syndrome (1 variants)
  • Dyslexia,_susceptibility_to,_2 (1 variants)
  • Chylomicron_retention_disease (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DCDC2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000016356.5. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
7
clinvar
50
clinvar
 57
missense
2
clinvar
2
clinvar
142
clinvar
12
clinvar
 158
nonsense
3
clinvar
5
clinvar
2
clinvar
 10
start loss
0
frameshift
4
clinvar
7
clinvar
1
clinvar
 12
splice donor/acceptor (+/-2bp)
4
clinvar
3
clinvar
1
clinvar
 8
Total 13 17 153 62 0

Highest pathogenic variant AF is 0.0000340785

Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
DCDC2protein_codingprotein_codingENST00000378454 10186297
pLI Probability
LOF Intolerant 		pRec Probability
LOF Recessive 		Individuals with
no LOFs 		Individuals with
Homozygous LOFs 		Individuals with
Heterozygous LOFs 		Defined p
5.66e-100.3961256930551257480.000219
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense0.4322522720.9260.00001493131
Missense in Polyphen6888.9620.76437957
Synonymous-0.9011161041.110.00000613908
Loss of Function0.9981722.10.7719.80e-7288

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.0003870.000387
Ashkenazi Jewish0.0001010.0000992
East Asian0.0001680.000163
Finnish0.0002840.000277
European (Non-Finnish)0.0002590.000255
Middle Eastern0.0001680.000163
South Asian0.0001310.000131
Other0.0003380.000326

dbNSFP

Source: dbNSFP

Function
FUNCTION: Protein that plays a role in the inhibition of canonical Wnt signaling pathway (PubMed:25557784). May be involved in neuronal migration during development of the cerebral neocortex (By similarity). Involved in the control of ciliogenesis and ciliary length (PubMed:25601850, PubMed:27319779). {ECO:0000250|UniProtKB:D3ZR10, ECO:0000269|PubMed:25557784, ECO:0000269|PubMed:25601850, ECO:0000269|PubMed:27319779}.;
Disease
DISEASE: Nephronophthisis 19 (NPHP19) [MIM:616217]: A form of nephronophthisis, an autosomal recessive disorder characterized by chronic tubulointerstitial nephritis resulting in end-stage renal disease. NPHP19 patients also manifest hepatosplenomegaly, hepatic fibrosis, destruction of the bile ducts, focal bile ductal proliferation, ductal plate malformation, and cholestasis. {ECO:0000269|PubMed:25557784}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Deafness, autosomal recessive, 66 (DFNB66) [MIM:610212]: A form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. {ECO:0000269|PubMed:25601850}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Sclerosing cholangitis, neonatal (NSC) [MIM:617394]: An autosomal recessive form of liver disease with onset in infancy. Affected infants have jaundice, cholestasis, acholic stools, and progressive liver dysfunction resulting in fibrosis and cirrhosis. Cholangiography shows patent biliary ducts, but there are bile duct irregularities. {ECO:0000269|PubMed:27319779, ECO:0000269|PubMed:27469900}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Intolerance Scores

loftool
0.473
rvis_EVS
0.86
rvis_percentile_EVS
88.74

Haploinsufficiency Scores

pHI
0.0421
hipred
N
hipred_score
0.208
ghis

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
N
essential_gene_gene_trap
N
gene_indispensability_pred
E
gene_indispensability_score
0.817

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Dcdc2a
Phenotype
behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan);

Gene ontology

Biological process
neuron migration;cellular defense response;sensory perception of sound;regulation of Wnt signaling pathway;intracellular signal transduction;positive regulation of smoothened signaling pathway;dendrite morphogenesis;cilium assembly;regulation of cilium assembly
Cellular component
nucleoplasm;cytoplasm;microtubule organizing center;cytosol;microtubule;cilium;axoneme;microtubule cytoskeleton;cortical actin cytoskeleton;kinocilium;mitotic spindle
Molecular function
protein binding;kinesin binding