CEP290
centrosomal protein 290, the group of MKS complex
Basic information
Region (hg38): 12:88049015-88142099
Links
Phenotypes
GenCC
Source:
- Joubert syndrome 5 (Definitive), mode of inheritance: AR
- Bardet-Biedl syndrome 14 (Moderate), mode of inheritance: AR
- Meckel syndrome (Supportive), mode of inheritance: AR
- Joubert syndrome with oculorenal defect (Supportive), mode of inheritance: AR
- Senior-Loken syndrome (Supportive), mode of inheritance: AR
- Leber congenital amaurosis (Supportive), mode of inheritance: AD
- Bardet-Biedl syndrome (Supportive), mode of inheritance: AR
- Bardet-Biedl syndrome 14 (Strong), mode of inheritance: AR
- Joubert syndrome 5 (Strong), mode of inheritance: AR
- Leber congenital amaurosis 10 (Strong), mode of inheritance: AR
- CEP290-related ciliopathy (Definitive), mode of inheritance: AR
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Bardet-Biedl syndrome 14 | AR | Endocrine | Medical management of obesity with melanocortin-4 receptor (MC4R) agonist (setmelanotide) may be beneficial | Craniofacial; Endocrine; Gastrointestinal; Genitourinary; Musculoskeletal; Neurologic; Ophthalmologic; Pulmonary; Renal | 16909394; 16682973; 16682970; 17564974; 17564967; 17554762; 17617513; 17898177; 17705300; 18327255; 20301537; 20690115; 20805370; 36356613 |
ClinVar
This is a list of variants' phenotypes submitted to
- Nephronophthisis;Meckel-Gruber syndrome;Familial aplasia of the vermis (570 variants)
- Familial aplasia of the vermis;Meckel-Gruber syndrome;Nephronophthisis (569 variants)
- not provided (523 variants)
- Familial aplasia of the vermis;Nephronophthisis;Meckel-Gruber syndrome (460 variants)
- Bardet-Biedl syndrome 14 (446 variants)
- Leber congenital amaurosis (398 variants)
- Meckel-Gruber syndrome;Familial aplasia of the vermis;Nephronophthisis (339 variants)
- Meckel-Gruber syndrome;Nephronophthisis;Familial aplasia of the vermis (314 variants)
- Joubert syndrome 5 (211 variants)
- Nephronophthisis;Familial aplasia of the vermis;Meckel-Gruber syndrome (206 variants)
- Meckel syndrome, type 4 (170 variants)
- not specified (168 variants)
- Leber congenital amaurosis 10 (161 variants)
- Senior-Loken syndrome 6 (142 variants)
- CEP290-related condition (113 variants)
- Inborn genetic diseases (90 variants)
- Retinal dystrophy (42 variants)
- CEP290-Related Disorders (38 variants)
- Retinitis pigmentosa (22 variants)
- Meckel-Gruber syndrome (17 variants)
- Kidney disorder (16 variants)
- Joubert syndrome 1 (15 variants)
- Leber congenital amaurosis 10;Meckel syndrome, type 4;Senior-Loken syndrome 6;Joubert syndrome 5;Bardet-Biedl syndrome 14 (15 variants)
- Familial aplasia of the vermis (14 variants)
- Intellectual disability (12 variants)
- Renal dysplasia and retinal aplasia (12 variants)
- Bardet-Biedl syndrome (12 variants)
- Leber congenital amaurosis 10;Senior-Loken syndrome 6;Bardet-Biedl syndrome 14;Meckel syndrome, type 4;Joubert syndrome 5 (11 variants)
- Meckel syndrome, type 4;Leber congenital amaurosis 10;Senior-Loken syndrome 6;Joubert syndrome 5;Bardet-Biedl syndrome 14 (10 variants)
- Senior-Loken syndrome 6;Joubert syndrome 5;Bardet-Biedl syndrome 14;Leber congenital amaurosis 10;Meckel syndrome, type 4 (10 variants)
- Bardet-Biedl syndrome 14;Leber congenital amaurosis 10;Senior-Loken syndrome 6;Joubert syndrome 5;Meckel syndrome, type 4 (9 variants)
- Leber congenital amaurosis 10;Senior-Loken syndrome 6;Joubert syndrome 5;Meckel syndrome, type 4;Bardet-Biedl syndrome 14 (9 variants)
- Bardet-Biedl syndrome 14;Leber congenital amaurosis 10;Meckel syndrome, type 4;Senior-Loken syndrome 6;Joubert syndrome 5 (8 variants)
- Joubert syndrome 5;Senior-Loken syndrome 6;Bardet-Biedl syndrome 14;Leber congenital amaurosis 10;Meckel syndrome, type 4 (8 variants)
- Leber congenital amaurosis 10;Meckel syndrome, type 4;Joubert syndrome 5;Bardet-Biedl syndrome 14;Senior-Loken syndrome 6 (8 variants)
- Leber congenital amaurosis 10;Meckel syndrome, type 4;Joubert syndrome 5;Senior-Loken syndrome 6;Bardet-Biedl syndrome 14 (7 variants)
- Meckel syndrome, type 4;Bardet-Biedl syndrome 14;Leber congenital amaurosis 10;Senior-Loken syndrome 6;Joubert syndrome 5 (7 variants)
- CEP290-related ciliopathy (7 variants)
- Leber congenital amaurosis 10;Meckel syndrome, type 4;Senior-Loken syndrome 6;Bardet-Biedl syndrome 14;Joubert syndrome 5 (6 variants)
- Meckel syndrome, type 4;Senior-Loken syndrome 6;Bardet-Biedl syndrome 14;Leber congenital amaurosis 10;Joubert syndrome 5 (6 variants)
- Senior-Loken syndrome 6;Bardet-Biedl syndrome 14;Leber congenital amaurosis 10;Meckel syndrome, type 4;Joubert syndrome 5 (6 variants)
- Bardet-Biedl syndrome 14;Senior-Loken syndrome 6;Joubert syndrome 5;Leber congenital amaurosis 10;Meckel syndrome, type 4 (6 variants)
- Meckel syndrome, type 4;Leber congenital amaurosis 10;Senior-Loken syndrome 6;Bardet-Biedl syndrome 14;Joubert syndrome 5 (6 variants)
- Meckel syndrome, type 4;Leber congenital amaurosis 10;Joubert syndrome 5;Bardet-Biedl syndrome 14;Senior-Loken syndrome 6 (6 variants)
- Leber congenital amaurosis 10;Senior-Loken syndrome 6;Joubert syndrome 5;Bardet-Biedl syndrome 14;Meckel syndrome, type 4 (6 variants)
- Meckel syndrome, type 4;Bardet-Biedl syndrome 14;Joubert syndrome 5;Leber congenital amaurosis 10;Senior-Loken syndrome 6 (5 variants)
- Joubert syndrome 5;Bardet-Biedl syndrome 14;Leber congenital amaurosis 10;Meckel syndrome, type 4;Senior-Loken syndrome 6 (5 variants)
- Leber congenital amaurosis 10;Joubert syndrome 5;Bardet-Biedl syndrome 14;Meckel syndrome, type 4;Senior-Loken syndrome 6 (5 variants)
- Meckel syndrome, type 4;Leber congenital amaurosis 10;Bardet-Biedl syndrome 14;Senior-Loken syndrome 6;Joubert syndrome 5 (5 variants)
- Leber congenital amaurosis 10;Senior-Loken syndrome 6;Meckel syndrome, type 4;Bardet-Biedl syndrome 14;Joubert syndrome 5 (5 variants)
- Joubert syndrome 5;Bardet-Biedl syndrome 14;Meckel syndrome, type 4;Leber congenital amaurosis 10;Senior-Loken syndrome 6 (4 variants)
- Rod-cone dystrophy (4 variants)
- Leber congenital amaurosis 10;Meckel syndrome, type 4;Bardet-Biedl syndrome 14;Senior-Loken syndrome 6;Joubert syndrome 5 (4 variants)
- Leber congenital amaurosis 10;Meckel syndrome, type 4;Joubert syndrome 5;Senior-Loken syndrome 6 (4 variants)
- Senior-Loken syndrome 6;Bardet-Biedl syndrome 14;Joubert syndrome 5;Leber congenital amaurosis 10;Meckel syndrome, type 4 (4 variants)
- Meckel syndrome, type 4;Joubert syndrome 5;Bardet-Biedl syndrome 14;Senior-Loken syndrome 6;Leber congenital amaurosis 10 (4 variants)
- Meckel syndrome, type 4;Joubert syndrome 5;Bardet-Biedl syndrome 14;Leber congenital amaurosis 10;Senior-Loken syndrome 6 (4 variants)
- Meckel syndrome, type 4;Senior-Loken syndrome 6;Joubert syndrome 5;Leber congenital amaurosis 10;Bardet-Biedl syndrome 14 (3 variants)
- Senior-Loken syndrome 6;Joubert syndrome 5;Leber congenital amaurosis 10;Bardet-Biedl syndrome 14;Meckel syndrome, type 4 (3 variants)
- Nephronophthisis (3 variants)
- Joubert syndrome 5;Senior-Loken syndrome 6;Leber congenital amaurosis 10;Meckel syndrome, type 4;Bardet-Biedl syndrome 14 (3 variants)
- Joubert syndrome 5;Bardet-Biedl syndrome 14;Senior-Loken syndrome 6;Leber congenital amaurosis 10;Meckel syndrome, type 4 (3 variants)
- Leber congenital amaurosis 10;Meckel syndrome, type 4;Bardet-Biedl syndrome 14;Joubert syndrome 5;Senior-Loken syndrome 6 (3 variants)
- Bardet-Biedl syndrome 14;Leber congenital amaurosis 10;Meckel syndrome, type 4;Joubert syndrome 5;Senior-Loken syndrome 6 (3 variants)
- Meckel syndrome, type 4;Senior-Loken syndrome 6;Leber congenital amaurosis 10;Joubert syndrome 5;Bardet-Biedl syndrome 14 (3 variants)
- Senior-Loken syndrome 6;Leber congenital amaurosis 10;Meckel syndrome, type 4;Joubert syndrome 5 (3 variants)
- Senior-Loken syndrome 6;Bardet-Biedl syndrome 14;Meckel syndrome, type 4;Leber congenital amaurosis 10;Joubert syndrome 5 (3 variants)
- Joubert syndrome 5;Leber congenital amaurosis 10;Meckel syndrome, type 4;Senior-Loken syndrome 6;Bardet-Biedl syndrome 14 (3 variants)
- Senior-Loken syndrome 6;Bardet-Biedl syndrome 14;Meckel syndrome, type 4;Joubert syndrome 5;Leber congenital amaurosis 10 (3 variants)
- Meckel syndrome, type 6 (3 variants)
- Bardet-Biedl syndrome 14;Joubert syndrome 5;Leber congenital amaurosis 10;Meckel syndrome, type 4;Senior-Loken syndrome 6 (3 variants)
- Bardet-Biedl syndrome 14;Meckel syndrome, type 4;Senior-Loken syndrome 6;Joubert syndrome 5;Leber congenital amaurosis 10 (3 variants)
- Meckel syndrome, type 4;Bardet-Biedl syndrome 14;Senior-Loken syndrome 6;Joubert syndrome 5;Leber congenital amaurosis 10 (3 variants)
- Leber congenital amaurosis 10;Bardet-Biedl syndrome 14;Meckel syndrome, type 4;Senior-Loken syndrome 6;Joubert syndrome 5 (3 variants)
- Senior-Loken syndrome 6;Leber congenital amaurosis 10;Bardet-Biedl syndrome 14;Meckel syndrome, type 4;Joubert syndrome 5 (3 variants)
- Senior-Loken syndrome 6;Bardet-Biedl syndrome 14;Joubert syndrome 5;Meckel syndrome, type 4;Leber congenital amaurosis 10 (3 variants)
- Senior-Loken syndrome 6;Leber congenital amaurosis 10;Meckel syndrome, type 4;Joubert syndrome 5;Bardet-Biedl syndrome 14 (3 variants)
- See cases (2 variants)
- Senior-Loken syndrome 6;Joubert syndrome 5;Bardet-Biedl syndrome 14;Meckel syndrome, type 4;Leber congenital amaurosis 10 (2 variants)
- Bardet-Biedl syndrome 14;Senior-Loken syndrome 6;Leber congenital amaurosis 10;Meckel syndrome, type 4;Joubert syndrome 5 (2 variants)
- Leber congenital amaurosis 10;Senior-Loken syndrome 6;Bardet-Biedl syndrome 14;Joubert syndrome 5;Meckel syndrome, type 4 (2 variants)
- Stuve-Wiedemann syndrome 2 (2 variants)
- Abnormality of the nervous system (2 variants)
- Bardet-Biedl syndrome 14;Meckel syndrome, type 4;Joubert syndrome 5;Leber congenital amaurosis 10;Senior-Loken syndrome 6 (2 variants)
- Bardet-Biedl syndrome 14;Meckel syndrome, type 4;Leber congenital amaurosis 10;Joubert syndrome 5;Senior-Loken syndrome 6 (2 variants)
- 6 conditions (2 variants)
- Blindness (2 variants)
- Severe hydrocephalus;Polycystic kidney disease;Encephalocele (2 variants)
- Joubert syndrome 5;Bardet-Biedl syndrome 14 (2 variants)
- Senior-Loken syndrome 6;Meckel syndrome, type 4;Bardet-Biedl syndrome 14;Leber congenital amaurosis 10;Joubert syndrome 5 (2 variants)
- Senior-Loken syndrome 6;Leber congenital amaurosis 10;Meckel syndrome, type 4;Bardet-Biedl syndrome 14;Joubert syndrome 5 (2 variants)
- Senior-Loken syndrome 6;Joubert syndrome 5;Meckel syndrome, type 4;Leber congenital amaurosis 10 (2 variants)
- Meckel syndrome, type 4;Senior-Loken syndrome 6;Joubert syndrome 5;Bardet-Biedl syndrome 14;Leber congenital amaurosis 10 (2 variants)
- Senior-Loken syndrome 6;Joubert syndrome 5;Meckel syndrome, type 4;Bardet-Biedl syndrome 14;Leber congenital amaurosis 10 (2 variants)
- Occipital encephalocele;Cystic renal dysplasia (2 variants)
- Abnormality of prenatal development or birth (2 variants)
- Bardet-Biedl syndrome 14;Senior-Loken syndrome 6;Joubert syndrome 5;Meckel syndrome, type 4;Leber congenital amaurosis 10 (2 variants)
- Meckel syndrome, type 4;Bardet-Biedl syndrome 14;Senior-Loken syndrome 6;Leber congenital amaurosis 10;Joubert syndrome 5 (2 variants)
- Joubert syndrome 5;Meckel syndrome, type 4;Senior-Loken syndrome 6;Leber congenital amaurosis 10;Bardet-Biedl syndrome 14 (2 variants)
- Central hypotonia;Molar tooth sign on MRI;Nystagmus (2 variants)
- Senior-Loken syndrome 6;Leber congenital amaurosis 10;Bardet-Biedl syndrome 14;Joubert syndrome 5;Meckel syndrome, type 4 (1 variants)
- Senior-Loken syndrome 6;Meckel syndrome, type 4;Bardet-Biedl syndrome 14;Joubert syndrome 5 (1 variants)
- Meckel syndrome, type 4;Joubert syndrome 5;Leber congenital amaurosis 10;Senior-Loken syndrome 6 (1 variants)
- Microcephaly (1 variants)
- Meckel syndrome, type 4;Leber congenital amaurosis 10;Joubert syndrome 5;Senior-Loken syndrome 6 (1 variants)
- Joubert syndrome 5;Leber congenital amaurosis 10;Meckel syndrome, type 4;Senior-Loken syndrome 6 (1 variants)
- Leber congenital amaurosis 10;Joubert syndrome 5;Bardet-Biedl syndrome 14;Senior-Loken syndrome 6;Meckel syndrome, type 4 (1 variants)
- Senior-Loken syndrome 6;Bardet-Biedl syndrome 14;Meckel syndrome, type 4;Joubert syndrome 5 (1 variants)
- Congenital blindness (1 variants)
- Senior-Loken syndrome 6;Meckel syndrome, type 4;Joubert syndrome 5;Leber congenital amaurosis 10;Bardet-Biedl syndrome 14 (1 variants)
- Bardet-Biedl syndrome 14;Leber congenital amaurosis 10;Joubert syndrome 5;Senior-Loken syndrome 6;Meckel syndrome, type 4 (1 variants)
- Meckel syndrome, type 4;Senior-Loken syndrome 6;Joubert syndrome 5 (1 variants)
- Leber congenital amaurosis 10;Senior-Loken syndrome 6;Meckel syndrome, type 4;Joubert syndrome 5 (1 variants)
- Meckel syndrome, type 4;Joubert syndrome 5;Senior-Loken syndrome 6;Leber congenital amaurosis 10 (1 variants)
- - (1 variants)
- COG7 congenital disorder of glycosylation (1 variants)
- Senior-Loken syndrome 6;Joubert syndrome 5;Leber congenital amaurosis 10;Meckel syndrome, type 4 (1 variants)
- CEP290-related ciliopathies (1 variants)
- Joubert syndrome 5;Leber congenital amaurosis 10;Meckel syndrome, type 4;Bardet-Biedl syndrome 14;Senior-Loken syndrome 6 (1 variants)
- Joubert syndrome 5;Leber congenital amaurosis 10;Senior-Loken syndrome 6;Bardet-Biedl syndrome 14;Meckel syndrome, type 4 (1 variants)
- Blindness;Global developmental delay (1 variants)
- Leber congenital amaurosis 10;Bardet-Biedl syndrome 14;Meckel syndrome, type 4;Joubert syndrome 5;Senior-Loken syndrome 6 (1 variants)
- Occipital encephalocele (1 variants)
- Bardet-Biedl syndrome 14;Meckel syndrome, type 4;Leber congenital amaurosis 10;Senior-Loken syndrome 6;Joubert syndrome 5 (1 variants)
- Spastic ataxia (1 variants)
- Leber congenital amaurosis 10;Joubert syndrome 5;Meckel syndrome, type 4;Senior-Loken syndrome 6 (1 variants)
- Bardet-Biedl syndrome 14;Joubert syndrome 5 (1 variants)
- Leber congenital amaurosis 10;Meckel syndrome, type 4;Senior-Loken syndrome 6;Joubert syndrome 5 (1 variants)
- Meckel syndrome, type 4;Joubert syndrome 5;Senior-Loken syndrome 6;Leber congenital amaurosis 10;Bardet-Biedl syndrome 14 (1 variants)
- Senior-Loken syndrome 6;Meckel syndrome, type 4;Bardet-Biedl syndrome 14;Joubert syndrome 5;Leber congenital amaurosis 10 (1 variants)
- Joubert syndrome 5;Senior-Loken syndrome 6;Leber congenital amaurosis 10;Bardet-Biedl syndrome 14;Meckel syndrome, type 4 (1 variants)
- Retinopathy (1 variants)
- Meckel syndrome, type 4;Bardet-Biedl syndrome 14;Joubert syndrome 5;Senior-Loken syndrome 6 (1 variants)
- Meckel syndrome, type 4;Joubert syndrome 5;Leber congenital amaurosis 10;Bardet-Biedl syndrome 14;Senior-Loken syndrome 6 (1 variants)
- Night blindness (1 variants)
- Meckel syndrome, type 4;Senior-Loken syndrome 6;Leber congenital amaurosis 10;Joubert syndrome 5 (1 variants)
- Meckel syndrome, type 4;Leber congenital amaurosis 10;Joubert syndrome 5;Senior-Loken syndrome 6;Bardet-Biedl syndrome 14 (1 variants)
- Joubert syndrome 5;Renal dysplasia and retinal aplasia;Leber congenital amaurosis 10;Meckel syndrome, type 4 (1 variants)
- Global developmental delay;Blindness (1 variants)
- Leber congenital amaurosis 10;Senior-Loken syndrome 6;Joubert syndrome 5;Meckel syndrome, type 4 (1 variants)
- Senior-Loken syndrome 6;Meckel syndrome, type 4;Leber congenital amaurosis 10;Bardet-Biedl syndrome 14;Joubert syndrome 5 (1 variants)
- Senior-Loken syndrome 6;Joubert syndrome 5 (1 variants)
- Hypotonia;Abnormal facial shape;Micrognathia;Global developmental delay (1 variants)
- Joubert syndrome 5;Senior-Loken syndrome 6;Leber congenital amaurosis 10;Meckel syndrome, type 4 (1 variants)
- Senior-Loken syndrome 6;Leber congenital amaurosis 10;Joubert syndrome 5;Meckel syndrome, type 4;Bardet-Biedl syndrome 14 (1 variants)
- Bardet-Biedl syndrome 14;Joubert syndrome 5;Senior-Loken syndrome 6;Leber congenital amaurosis 10;Meckel syndrome, type 4 (1 variants)
- Senior-Loken syndrome 6;Joubert syndrome 5;Leber congenital amaurosis 10;Meckel syndrome, type 4;Bardet-Biedl syndrome 14 (1 variants)
- Atypical hemolytic-uremic syndrome (1 variants)
- Bardet-Biedl syndrome 14;Meckel syndrome, type 4;Senior-Loken syndrome 6;Leber congenital amaurosis 10;Joubert syndrome 5 (1 variants)
- Cone-rod dystrophy (1 variants)
- Meckel syndrome, type 4;Joubert syndrome 5;Leber congenital amaurosis 10;Senior-Loken syndrome 6;Bardet-Biedl syndrome 14 (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the CEP290 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 | 625 | 635 | ||||
| missense | 896 | 11 | 922 | |||
| nonsense | 135 | 73 | 208 | |||
| start loss | 4 | |||||
| frameshift | 160 | 125 | 288 | |||
| inframe indel | 28 | 28 | ||||
| splice donor/acceptor (+/-2bp) | 28 | 75 | 105 | |||
| splice region ? | 2 | 4 | 44 | 140 | 7 | 197 |
| non coding ? | 22 | 320 | 78 | 424 | ||
| Total | 328 | 285 | 958 | 957 | 86 |
Highest pathogenic variant AF is 0.0000923
Variants in CEP290
This is a list of pathogenic ClinVar variants found in the CEP290 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 12-88049016-T-C | Meckel syndrome, type 4 • Bardet-Biedl syndrome 14 • Leber congenital amaurosis 10 • Joubert syndrome 5 • Senior-Loken syndrome 6 | Uncertain significance (Jan 12, 2018) | ||
| 12-88049033-A-G | Joubert syndrome 5 • Meckel syndrome, type 4 • Bardet-Biedl syndrome 14 • Senior-Loken syndrome 6 • Leber congenital amaurosis 10 | Uncertain significance (Jan 12, 2018) | ||
| 12-88049037-TTTTA-T | Renal dysplasia and retinal aplasia • Leber congenital amaurosis • Familial aplasia of the vermis • Meckel-Gruber syndrome • Bardet-Biedl syndrome | Uncertain significance (Jun 14, 2016) | ||
| 12-88049140-A-T | not specified | Likely benign (-) | ||
| 12-88049161-GAAAC-G | not specified • Bardet-Biedl syndrome • Renal dysplasia and retinal aplasia • Meckel-Gruber syndrome • Familial aplasia of the vermis • Leber congenital amaurosis | Benign/Likely benign (May 10, 2018) | ||
| 12-88049187-G-A | Meckel-Gruber syndrome;Familial aplasia of the vermis;Nephronophthisis | Likely benign (Mar 04, 2022) | ||
| 12-88049194-G-C | Meckel-Gruber syndrome;Nephronophthisis;Familial aplasia of the vermis | Uncertain significance (Jun 29, 2022) | ||
| 12-88049199-A-G | Nephronophthisis;Familial aplasia of the vermis;Meckel-Gruber syndrome | Likely benign (Sep 27, 2022) | ||
| 12-88049202-A-G | Nephronophthisis;Meckel-Gruber syndrome;Familial aplasia of the vermis | Likely benign (Sep 26, 2023) | ||
| 12-88049208-A-G | Meckel-Gruber syndrome;Familial aplasia of the vermis;Nephronophthisis | Likely benign (Aug 20, 2022) | ||
| 12-88049208-A-T | Meckel-Gruber syndrome;Nephronophthisis;Familial aplasia of the vermis | Uncertain significance (Aug 23, 2022) | ||
| 12-88049210-TTTC-T | Familial aplasia of the vermis;Meckel-Gruber syndrome;Nephronophthisis • Leber congenital amaurosis | Uncertain significance (Aug 31, 2021) | ||
| 12-88049211-TTC-T | Meckel-Gruber syndrome;Familial aplasia of the vermis;Nephronophthisis • CEP290-related disorder | Uncertain significance (Feb 01, 2024) | ||
| 12-88049213-C-T | Familial aplasia of the vermis;Meckel-Gruber syndrome;Nephronophthisis • Inborn genetic diseases • Retinal dystrophy | Uncertain significance (Nov 27, 2023) | ||
| 12-88049227-A-G | Meckel-Gruber syndrome;Familial aplasia of the vermis;Nephronophthisis • Leber congenital amaurosis | Uncertain significance (Sep 13, 2022) | ||
| 12-88049227-A-T | Meckel-Gruber syndrome;Familial aplasia of the vermis;Nephronophthisis • Inborn genetic diseases | Uncertain significance (Feb 22, 2023) | ||
| 12-88049226-A-AAACT | Meckel-Gruber syndrome;Familial aplasia of the vermis;Nephronophthisis | Uncertain significance (Aug 12, 2022) | ||
| 12-88049228-ACT-A | not specified • Bardet-Biedl syndrome 14 • Joubert syndrome 5 • Meckel-Gruber syndrome;Familial aplasia of the vermis;Nephronophthisis | Conflicting classifications of pathogenicity (Jan 27, 2024) | ||
| 12-88049228-A-ACTC | Nephronophthisis;Meckel-Gruber syndrome;Familial aplasia of the vermis | Uncertain significance (Aug 23, 2023) | ||
| 12-88049231-C-CTG | Familial aplasia of the vermis;Meckel-Gruber syndrome;Nephronophthisis • Leber congenital amaurosis • CEP290-related disorder | Uncertain significance (Dec 20, 2023) | ||
| 12-88049237-AAGC-A | Familial aplasia of the vermis;Meckel-Gruber syndrome;Nephronophthisis • Leber congenital amaurosis | Uncertain significance (Aug 31, 2022) | ||
| 12-88049238-A-C | Familial aplasia of the vermis;Nephronophthisis;Meckel-Gruber syndrome | Likely benign (Jul 25, 2022) | ||
| 12-88049244-A-T | Familial aplasia of the vermis;Nephronophthisis;Meckel-Gruber syndrome | Likely benign (Oct 16, 2023) | ||
| 12-88049249-G-A | Senior-Loken syndrome 6 • Bardet-Biedl syndrome 14 • Leber congenital amaurosis 10 • Joubert syndrome 5 • Meckel syndrome, type 4 • Meckel-Gruber syndrome;Nephronophthisis;Familial aplasia of the vermis | Uncertain significance (Jul 19, 2022) | ||
| 12-88049250-G-A | Meckel-Gruber syndrome;Nephronophthisis;Familial aplasia of the vermis | Likely benign (Oct 08, 2023) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| CEP290 | protein_coding | protein_coding | ENST00000552810 | 53 | 93201 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 1.05e-60 | 0.00000370 | 124266 | 0 | 373 | 124639 | 0.00150 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 0.475 | 949 | 991 | 0.958 | 0.0000493 | 16290 |
| Missense in Polyphen | 323 | 340.96 | 0.94734 | 5715 | ||
| Synonymous | 0.133 | 327 | 330 | 0.991 | 0.0000154 | 4071 |
| Loss of Function | 1.69 | 104 | 124 | 0.837 | 0.00000639 | 1986 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00212 | 0.00208 |
| Ashkenazi Jewish | 0.0000997 | 0.0000994 |
| East Asian | 0.00339 | 0.00334 |
| Finnish | 0.000469 | 0.000464 |
| European (Non-Finnish) | 0.00181 | 0.00172 |
| Middle Eastern | 0.00339 | 0.00334 |
| South Asian | 0.00168 | 0.00157 |
| Other | 0.00140 | 0.00132 |
dbNSFP
Source:
- Function
- FUNCTION: Involved in early and late steps in cilia formation. Its association with CCP110 is required for inhibition of primary cilia formation by CCP110 (PubMed:18694559). May play a role in early ciliogenesis in the disappearance of centriolar satellites and in the transition of primary ciliar vesicles (PCVs) to capped ciliary vesicles (CCVs). Required for the centrosomal recruitment of RAB8A and for the targeting of centriole satellite proteins to centrosomes such as of PCM1 (PubMed:24421332). Required for the correct localization of ciliary and phototransduction proteins in retinal photoreceptor cells; may play a role in ciliary transport processes (By similarity). Required for efficient recruitment of RAB8A to primary cilium (PubMed:17705300). In the ciliary transition zone is part of the tectonic-like complex which is required for tissue-specific ciliogenesis and may regulate ciliary membrane composition (By similarity). Involved in regulation of the BBSome complex integrity, specifically for presence of BBS2, BBS5 and BBS8/TTC8 in the complex, and in ciliary targeting of selected BBSome cargos. May play a role in controlling entry of the BBSome complex to cilia possibly implicating IQCB1/NPHP5 (PubMed:25552655). Activates ATF4-mediated transcription (PubMed:16682973). {ECO:0000250|UniProtKB:Q6A078, ECO:0000269|PubMed:16682973, ECO:0000269|PubMed:17705300, ECO:0000269|PubMed:18694559, ECO:0000269|PubMed:24421332, ECO:0000269|PubMed:25552655}.;
- Disease
- DISEASE: Joubert syndrome 5 (JBTS5) [MIM:610188]: A disorder presenting with cerebellar ataxia, oculomotor apraxia, hypotonia, neonatal breathing abnormalities and psychomotor delay. Neuroradiologically, it is characterized by cerebellar vermian hypoplasia/aplasia, thickened and reoriented superior cerebellar peduncles, and an abnormally large interpeduncular fossa, giving the appearance of a molar tooth on transaxial slices (molar tooth sign). Additional variable features include retinal dystrophy and renal disease. Joubert syndrome type 5 shares the neurologic and neuroradiologic features of Joubert syndrome together with severe retinal dystrophy and/or progressive renal failure characterized by nephronophthisis. {ECO:0000269|PubMed:16682970, ECO:0000269|PubMed:16682973, ECO:0000269|PubMed:22425360, ECO:0000269|PubMed:26166481, ECO:0000269|PubMed:26477546}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Senior-Loken syndrome 6 (SLSN6) [MIM:610189]: A renal- retinal disorder characterized by progressive wasting of the filtering unit of the kidney (nephronophthisis), with or without medullary cystic renal disease, and progressive eye disease. Typically this disorder becomes apparent during the first year of life. {ECO:0000269|PubMed:20683928}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Leber congenital amaurosis 10 (LCA10) [MIM:611755]: A severe dystrophy of the retina, typically becoming evident in the first years of life. Visual function is usually poor and often accompanied by nystagmus, sluggish or near-absent pupillary responses, photophobia, high hyperopia and keratoconus. {ECO:0000269|PubMed:16909394}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Meckel syndrome 4 (MKS4) [MIM:611134]: A disorder characterized by a combination of renal cysts and variably associated features including developmental anomalies of the central nervous system (typically encephalocele), hepatic ductal dysplasia and cysts, and polydactyly. {ECO:0000269|PubMed:17564974}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Note=Antibodies against CEP290 are present in sera from patients with cutaneous T-cell lymphomas, but not in the healthy control population. {ECO:0000269|PubMed:11149944}.; DISEASE: Bardet-Biedl syndrome 14 (BBS14) [MIM:615991]: A syndrome characterized by usually severe pigmentary retinopathy, early- onset obesity, polydactyly, hypogenitalism, renal malformation and mental retardation. Secondary features include diabetes mellitus, hypertension and congenital heart disease. Bardet-Biedl syndrome inheritance is autosomal recessive, but three mutated alleles (two at one locus, and a third at a second locus) may be required for clinical manifestation of some forms of the disease. {ECO:0000269|PubMed:18327255}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Pathways in clear cell renal cell carcinoma;Neutrophil degranulation;Innate Immune System;Immune System;Regulation of PLK1 Activity at G2/M Transition;Recruitment of mitotic centrosome proteins and complexes;Loss of Nlp from mitotic centrosomes;Loss of proteins required for interphase microtubule organization from the centrosome;Centrosome maturation;AURKA Activation by TPX2;G2/M Transition;Mitotic G2-G2/M phases;Recruitment of NuMA to mitotic centrosomes;Mitotic Prometaphase;M Phase;Cell Cycle;Cell Cycle, Mitotic;Anchoring of the basal body to the plasma membrane;Cilium Assembly;Organelle biogenesis and maintenance
(Consensus)
Recessive Scores
- pRec
- 0.311
Intolerance Scores
- loftool
- 0.693
- rvis_EVS
- 0.37
- rvis_percentile_EVS
- 75.31
Haploinsufficiency Scores
- pHI
- 0.484
- hipred
- N
- hipred_score
- 0.378
- ghis
- 0.575
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.907
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | High |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Cep290
- Phenotype
- craniofacial phenotype; homeostasis/metabolism phenotype; cellular phenotype; taste/olfaction phenotype; growth/size/body region phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; normal phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); reproductive system phenotype; vision/eye phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); renal/urinary system phenotype; skeleton phenotype; immune system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system phenotype; pigmentation phenotype;
Zebrafish Information Network
- Gene name
- cep290
- Affected structure
- pronephric tubule
- Phenotype tag
- abnormal
- Phenotype quality
- cystic
Gene ontology
- Biological process
- G2/M transition of mitotic cell cycle;regulation of G2/M transition of mitotic cell cycle;protein transport;hindbrain development;otic vesicle formation;eye photoreceptor cell development;neutrophil degranulation;positive regulation of transcription, DNA-templated;pronephros development;cilium assembly;regulation of establishment of protein localization;positive regulation of intracellular protein transport;ciliary basal body-plasma membrane docking
- Cellular component
- gamma-tubulin complex;extracellular region;nucleus;cytoplasm;centrosome;centriole;cytosol;membrane;photoreceptor connecting cilium;protein-containing complex;centriolar satellite;specific granule lumen;ciliary transition zone;MKS complex;ciliary basal body
- Molecular function
- protein binding;identical protein binding;microtubule minus-end binding