PDE6C
Basic information
Region (hg38): 10:93612537-93666010
Links
Phenotypes
GenCC
Source:
- cone dystrophy 4 (Strong), mode of inheritance: AR
- cone dystrophy (Supportive), mode of inheritance: AD
- achromatopsia (Supportive), mode of inheritance: AR
- cone dystrophy 4 (Strong), mode of inheritance: AR
- cone dystrophy 4 (Definitive), mode of inheritance: AR
- inherited retinal dystrophy (Definitive), mode of inheritance: AR
Clinical Genomic Database
Source:
Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
---|---|---|---|---|---|
Cone dystrophy 4 | AR | General | Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing | Ophthalmologic | 19887631; 19615668 |
ClinVar
This is a list of variants' phenotypes submitted to
- not provided (30 variants)
- Achromatopsia (7 variants)
- Cone dystrophy 4 (3 variants)
- Isolated macular dystrophy (1 variants)
- Achromatopsia 5 (1 variants)
- PDE6C-related disorder (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the PDE6C 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 | 114 | 123 | ||||
missense | 243 | 262 | ||||
nonsense | 12 | |||||
start loss | 0 | |||||
frameshift | 18 | 22 | ||||
inframe indel | 5 | |||||
splice donor/acceptor (+/-2bp) | 12 | 18 | ||||
splice region | 1 | 17 | 24 | 2 | 44 | |
non coding | 12 | 72 | 10 | 94 | ||
Total | 37 | 26 | 265 | 192 | 16 |
Highest pathogenic variant AF is 0.0000789
Variants in PDE6C
This is a list of pathogenic ClinVar variants found in the PDE6C region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
Position | Type | Phenotype | Significance | ClinVar |
---|---|---|---|---|
10-93612705-C-T | Achromatopsia • Cone dystrophy 4 | Uncertain significance (Jan 13, 2018) | ||
10-93612719-C-A | Achromatopsia • Cone dystrophy 4 | Uncertain significance (Jan 12, 2018) | ||
10-93612745-T-C | Inborn genetic diseases | Uncertain significance (Feb 16, 2023) | ||
10-93612749-C-G | Likely benign (Nov 17, 2022) | |||
10-93612749-C-T | Likely benign (Jan 17, 2024) | |||
10-93612750-G-A | Uncertain significance (Oct 04, 2022) | |||
10-93612758-A-T | Uncertain significance (Nov 27, 2023) | |||
10-93612761-C-A | Pathogenic (Jul 14, 2023) | |||
10-93612761-C-T | Likely benign (Apr 21, 2021) | |||
10-93612770-GA-AC | Uncertain significance (Nov 28, 2023) | |||
10-93612771-A-C | Inborn genetic diseases | Uncertain significance (Mar 29, 2023) | ||
10-93612773-C-A | Uncertain significance (May 08, 2022) | |||
10-93612782-T-G | Uncertain significance (Aug 05, 2022) | |||
10-93612801-AG-A | Achromatopsia | Pathogenic (Dec 01, 2017) | ||
10-93612802-G-C | Uncertain significance (Aug 23, 2021) | |||
10-93612810-C-A | Likely benign (Nov 01, 2022) | |||
10-93612810-C-T | Cone dystrophy 4 • Achromatopsia 5 | Pathogenic/Likely pathogenic (Nov 28, 2023) | ||
10-93612811-G-A | Uncertain significance (Jan 04, 2024) | |||
10-93612813-G-A | Uncertain significance (May 04, 2022) | |||
10-93612818-G-T | Uncertain significance (Jul 05, 2022) | |||
10-93612826-G-A | Achromatopsia • Cone dystrophy 4 | Uncertain significance (Mar 26, 2022) | ||
10-93612830-A-T | Uncertain significance (Mar 02, 2022) | |||
10-93612833-C-A | Likely benign (Oct 01, 2022) | |||
10-93612849-G-A | Cone dystrophy 4 • Achromatopsia • Inborn genetic diseases | Uncertain significance (Jan 03, 2024) | ||
10-93612855-G-T | Inborn genetic diseases | Uncertain significance (Mar 15, 2024) |
GnomAD
Source:
Gene | Type | Bio Type | Transcript | Coding Exons | Length |
---|---|---|---|---|---|
PDE6C | protein_coding | protein_coding | ENST00000371447 | 22 | 53423 |
pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
---|---|---|---|---|---|---|
2.32e-16 | 0.942 | 125669 | 0 | 79 | 125748 | 0.000314 |
Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
---|---|---|---|---|---|---|
Missense | 1.14 | 387 | 455 | 0.850 | 0.0000242 | 5716 |
Missense in Polyphen | 142 | 196.23 | 0.72365 | 2518 | ||
Synonymous | -1.31 | 190 | 168 | 1.13 | 0.00000966 | 1535 |
Loss of Function | 2.33 | 33 | 51.0 | 0.647 | 0.00000277 | 601 |
LoF frequencies by population
Ethnicity | Sum of pLOFs | p |
---|---|---|
African & African-American | 0.00113 | 0.00113 |
Ashkenazi Jewish | 0.0000993 | 0.0000992 |
East Asian | 0.000272 | 0.000272 |
Finnish | 0.00 | 0.00 |
European (Non-Finnish) | 0.000229 | 0.000229 |
Middle Eastern | 0.000272 | 0.000272 |
South Asian | 0.000494 | 0.000490 |
Other | 0.000327 | 0.000326 |
dbNSFP
Source:
- Function
- FUNCTION: As cone-specific cGMP phosphodiesterase, it plays an essential role in light detection and cone phototransduction by rapidly decreasing intracellular levels of cGMP. {ECO:0000269|PubMed:21127010, ECO:0000269|PubMed:28583373}.;
- Disease
- DISEASE: Cone dystrophy 4 (COD4) [MIM:613093]: An early-onset cone dystrophy. Cone dystrophies are retinal dystrophies characterized by progressive degeneration of the cone photoreceptors with preservation of rod function, as indicated by electroretinogram. However, some rod involvement may be present in some cone dystrophies, particularly at late stage. Affected individuals suffer from photophobia, loss of visual acuity, color vision and central visual field. Another sign is the absence of macular lesions for many years. Cone dystrophies are distinguished from the cone-rod dystrophies in which some loss of peripheral vision also occurs. {ECO:0000269|PubMed:19615668}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Achromatopsia 5 (ACHM5) [MIM:613093]: A form of achromatopsia, an ocular stationary disorder due to the absence of functioning cone photoreceptors in the retina. It is characterized by total colorblindness, low visual acuity, photophobia and nystagmus. ACHM5 inheritance is autosomal recessive. {ECO:0000269|PubMed:19615668, ECO:0000269|PubMed:21127010, ECO:0000269|PubMed:28583373}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Purine metabolism - Homo sapiens (human);Phosphodiesterases in neuronal function;Purine metabolism;Purine nucleotides nucleosides metabolism;Visual signal transduction: Cones
(Consensus)
Recessive Scores
- pRec
- 0.133
Intolerance Scores
- loftool
- 0.816
- rvis_EVS
- 0.12
- rvis_percentile_EVS
- 62.17
Haploinsufficiency Scores
- pHI
- 0.349
- hipred
- N
- hipred_score
- 0.492
- ghis
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- N
- gene_indispensability_score
- 0.189
Gene Damage Prediction
All | Recessive | Dominant | |
---|---|---|---|
Mendelian | Medium | Medium | Medium |
Primary Immunodeficiency | Medium | Medium | High |
Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Pde6c
- 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);
Zebrafish Information Network
- Gene name
- pde6c
- Affected structure
- ON-bipolar cell
- Phenotype tag
- abnormal
- Phenotype quality
- morphology
Gene ontology
- Biological process
- visual perception;phototransduction, visible light;retinal cone cell development
- Cellular component
- plasma membrane
- Molecular function
- cGMP binding;metal ion binding;3',5'-cyclic-GMP phosphodiesterase activity