DCDC2

doublecortin domain containing 2, the group of Doublecortin superfamily

Basic information

Region (hg38): 6:24171754-24358059

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
• nonsyndromic genetic hearing loss (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Deafness, autosomal recessive 66; Nephronophthisis 19; Sclerosing cholangitis, neonatal	AR	Audiologic/Otolaryngologic; Gastrointestinal	Early 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 management	Audiologic/Otolaryngologic; Gastrointestinal; Renal	16244493; 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.

• not provided (131 variants)
• Autosomal recessive nonsyndromic hearing loss 66;Isolated neonatal sclerosing cholangitis (66 variants)
• Isolated neonatal sclerosing cholangitis;Autosomal recessive nonsyndromic hearing loss 66 (50 variants)
• Inborn genetic diseases (19 variants)
• not specified (14 variants)
• Isolated neonatal sclerosing cholangitis (11 variants)
• Nephronophthisis 19 (9 variants)
• Autosomal recessive nonsyndromic hearing loss 66 (8 variants)
• Autosomal recessive nonsyndromic hearing loss 66;Nephronophthisis 19;Isolated neonatal sclerosing cholangitis (6 variants)
• Isolated neonatal sclerosing cholangitis;Nephronophthisis 19;Autosomal recessive nonsyndromic hearing loss 66 (5 variants)
• DCDC2-related condition (5 variants)
• Autosomal recessive nonsyndromic hearing loss 66;Isolated neonatal sclerosing cholangitis;Nephronophthisis 19 (5 variants)
• Nephronophthisis 19;Autosomal recessive nonsyndromic hearing loss 66;Isolated neonatal sclerosing cholangitis (5 variants)
• Nephronophthisis 19;Isolated neonatal sclerosing cholangitis;Autosomal recessive nonsyndromic hearing loss 66 (3 variants)
• Chylomicron retention disease (1 variants)
• Dyslexia, susceptibility to, 2 (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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			5	23	3	31
missense			73	6	3	82
nonsense	2	2	1			5
start loss						0
frameshift	4	4		1		9
inframe indel			1			1
splice donor/acceptor (+/-2bp)	4	1				5
splice region				4		4
non coding			7	29	39	75
Total	10	7	87	59	45

Highest pathogenic variant AF is 0.0000131

Variants in DCDC2

This is a list of pathogenic ClinVar variants found in the DCDC2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
6-24174446-A-G			Benign (Apr 10, 2019)
6-24174451-T-TTACAAA			Benign (Nov 11, 2018)
6-24174575-A-C			Benign (Mar 31, 2019)
6-24174606-T-A			Benign (Jun 24, 2018)
6-24174720-T-C		DCDC2-related disorder	Likely benign (Sep 27, 2023)
6-24174727-G-A			Likely benign (May 10, 2017)
6-24174727-G-C		Isolated neonatal sclerosing cholangitis • Nephronophthisis 19 • Autosomal recessive nonsyndromic hearing loss 66	Benign (Jul 30, 2021)
6-24174738-C-T		Autosomal recessive nonsyndromic hearing loss 66;Isolated neonatal sclerosing cholangitis • DCDC2-related disorder	Conflicting classifications of pathogenicity (Dec 28, 2022)
6-24174739-G-A		Autosomal recessive nonsyndromic hearing loss 66;Isolated neonatal sclerosing cholangitis	Likely benign (Dec 19, 2023)
6-24174755-T-G		Autosomal recessive nonsyndromic hearing loss 66;Isolated neonatal sclerosing cholangitis	Uncertain significance (Oct 18, 2022)
6-24174771-C-T			Uncertain significance (Aug 04, 2017)
6-24174783-G-A			Uncertain significance (Apr 09, 2018)
6-24174793-T-A		not specified • Autosomal recessive nonsyndromic hearing loss 66;Isolated neonatal sclerosing cholangitis	Benign (Jan 31, 2024)
6-24174797-A-G		Isolated neonatal sclerosing cholangitis;Autosomal recessive nonsyndromic hearing loss 66;Nephronophthisis 19 • Inborn genetic diseases	Uncertain significance (Feb 12, 2024)
6-24174802-T-C		Autosomal recessive nonsyndromic hearing loss 66;Isolated neonatal sclerosing cholangitis • DCDC2-related disorder	Conflicting classifications of pathogenicity (Jan 06, 2024)
6-24174805-C-T			Uncertain significance (Nov 02, 2017)
6-24174813-G-T			Uncertain significance (Feb 14, 2023)
6-24174817-T-C		Isolated neonatal sclerosing cholangitis;Autosomal recessive nonsyndromic hearing loss 66	Likely benign (Jan 23, 2023)
6-24174819-G-T		DCDC2-related disorder	Uncertain significance (Sep 22, 2023)
6-24174843-A-G		DCDC2-related disorder	Likely benign (Mar 05, 2021)
6-24174845-A-G			Uncertain significance (Jan 02, 2020)
6-24174849-A-T		Autosomal recessive nonsyndromic hearing loss 66;Isolated neonatal sclerosing cholangitis	Likely benign (Nov 28, 2023)
6-24174896-T-C			Benign (Jun 16, 2018)
6-24175091-A-G			Benign (Dec 17, 2018)
6-24175094-CTTTA-C			Benign (Nov 29, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DCDC2	protein_coding	protein_coding	ENST00000378454	10	186297

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
5.66e-10	0.396	125693	0	55	125748	0.000219

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.432	252	272	0.926	0.0000149	3131
Missense in Polyphen		68	88.962	0.76437		957
Synonymous	-0.901	116	104	1.11	0.00000613	908
Loss of Function	0.998	17	22.1	0.771	9.80e-7	288

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000387	0.000387
Ashkenazi Jewish	0.000101	0.0000992
East Asian	0.000168	0.000163
Finnish	0.000284	0.000277
European (Non-Finnish)	0.000259	0.000255
Middle Eastern	0.000168	0.000163
South Asian	0.000131	0.000131
Other	0.000338	0.000326

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

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

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

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