C2
Basic information
Region (hg38): 6:31897785-31945673
Links
Phenotypes
GenCC
Source:
- complement component 2 deficiency (Strong), mode of inheritance: AR
Clinical Genomic Database
Source:
Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
---|---|---|---|---|---|
Complement component 2 deficiency | AR | Allergy/Immunology/Infectious | Antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial for infectious manifestations; Patients may also develop autoimmune manifestations, and treatment with immune modulators has been described | Allergy/Immunology/Infectious; Renal | 14446782; 4161820; 1124106; 2582254; 1542325; 1361318; 1577763; 8621452; 15643297; 16026838; 20417301; 20890976; 22842196 |
ClinVar
This is a list of variants' phenotypes submitted to
- not provided (9 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the C2 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 | 69 | 75 | ||||
missense | 145 | 152 | ||||
nonsense | 6 | |||||
start loss | 0 | |||||
frameshift | 6 | |||||
inframe indel | 0 | |||||
splice donor/acceptor (+/-2bp) | 7 | |||||
splice region | 8 | 7 | 15 | |||
non coding | 21 | 35 | 62 | |||
Total | 9 | 8 | 171 | 112 | 8 |
Highest pathogenic variant AF is 0.00000657
Variants in C2
This is a list of pathogenic ClinVar variants found in the C2 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
Position | Type | Phenotype | Significance | ClinVar |
---|---|---|---|---|
6-31900037-G-C | Benign (Feb 01, 2024) | |||
6-31900172-C-T | not specified | Uncertain significance (Jan 23, 2023) | ||
6-31900290-G-A | not specified | Uncertain significance (Apr 09, 2024) | ||
6-31900393-G-A | not specified | Uncertain significance (May 16, 2024) | ||
6-31900484-T-G | not specified | Uncertain significance (Mar 29, 2022) | ||
6-31900525-C-A | not specified | Uncertain significance (Feb 22, 2023) | ||
6-31900549-G-C | not specified | Uncertain significance (Jun 22, 2021) | ||
6-31900695-T-C | not specified | Uncertain significance (Aug 15, 2023) | ||
6-31900739-G-C | not specified | Uncertain significance (May 23, 2024) | ||
6-31900786-G-A | not specified | Uncertain significance (Dec 06, 2023) | ||
6-31900827-G-A | not specified | Uncertain significance (Oct 10, 2023) | ||
6-31900888-C-T | not specified | Uncertain significance (Jun 09, 2022) | ||
6-31901066-G-A | ZBTB12-related disorder • C2-related disorder | Benign (Jul 11, 2019) | ||
6-31901274-T-C | not specified | Uncertain significance (Dec 28, 2023) | ||
6-31901288-T-A | not specified | Uncertain significance (Jan 19, 2024) | ||
6-31927608-A-C | Age related macular degeneration 14 • Complement component 2 deficiency | Likely benign (Apr 27, 2017) | ||
6-31927716-C-A | Age related macular degeneration 14 • Complement component 2 deficiency | Uncertain significance (Jan 13, 2018) | ||
6-31927717-G-A | Complement component 2 deficiency • Age related macular degeneration 14 | Uncertain significance (Jan 12, 2018) | ||
6-31927732-G-A | Age related macular degeneration 14 • Complement component 2 deficiency | Uncertain significance (Jan 13, 2018) | ||
6-31927787-TC-T | Pathogenic (May 13, 2021) | |||
6-31927810-G-T | Likely benign (Nov 19, 2023) | |||
6-31927814-G-A | Benign (Jan 15, 2024) | |||
6-31927938-T-G | Likely benign (Jan 04, 2024) | |||
6-31927946-C-G | Uncertain significance (Mar 14, 2022) | |||
6-31927967-C-T | Uncertain significance (Mar 20, 2022) |
GnomAD
Source:
Gene | Type | Bio Type | Transcript | Coding Exons | Length |
---|---|---|---|---|---|
C2 | protein_coding | protein_coding | ENST00000299367 | 18 | 47888 |
pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
---|---|---|---|---|---|---|
1.35e-16 | 0.270 | 124496 | 2 | 1250 | 125748 | 0.00499 |
Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
---|---|---|---|---|---|---|
Missense | 1.12 | 361 | 426 | 0.847 | 0.0000266 | 4954 |
Missense in Polyphen | 128 | 169.65 | 0.75448 | 1985 | ||
Synonymous | 1.06 | 151 | 168 | 0.896 | 0.0000108 | 1478 |
Loss of Function | 1.42 | 30 | 39.6 | 0.757 | 0.00000232 | 421 |
LoF frequencies by population
Ethnicity | Sum of pLOFs | p |
---|---|---|
African & African-American | 0.00503 | 0.00501 |
Ashkenazi Jewish | 0.0115 | 0.0116 |
East Asian | 0.000273 | 0.000272 |
Finnish | 0.00520 | 0.00514 |
European (Non-Finnish) | 0.00726 | 0.00725 |
Middle Eastern | 0.000273 | 0.000272 |
South Asian | 0.000559 | 0.000555 |
Other | 0.00440 | 0.00441 |
dbNSFP
Source:
- Function
- FUNCTION: Component C2 which is part of the classical pathway of the complement system is cleaved by activated factor C1 into two fragments: C2b and C2a. C2a, a serine protease, then combines with complement factor C4b to generate the C3 or C5 convertase.;
- Disease
- DISEASE: Complement component 2 deficiency (C2D) [MIM:217000]: A rare defect of the complement classical pathway associated with the development of autoimmune disorders, mainly systemic lupus erythematosus. Skin and joint manifestations are common and renal disease is relatively rare. Patients with complement component 2 deficiency are also reported to have recurrent invasive infections. {ECO:0000269|PubMed:8621452, ECO:0000269|PubMed:9670930}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Complement and coagulation cascades - Homo sapiens (human);Pertussis - Homo sapiens (human);Systemic lupus erythematosus - Homo sapiens (human);Staphylococcus aureus infection - Homo sapiens (human);Allograft Rejection;Human Complement System;Dengue-2 Interactions with Complement and Coagulation Cascades;Oxidative Damage;Complement Activation;Complement and Coagulation Cascades;classical complement pathway;lectin induced complement pathway;Innate Immune System;Immune System;Activation of C3 and C5;Initial triggering of complement;Regulation of Complement cascade;Complement cascade
(Consensus)
Recessive Scores
- pRec
- 0.133
Intolerance Scores
- loftool
- 0.260
- rvis_EVS
- -0.07
- rvis_percentile_EVS
- 48.78
Haploinsufficiency Scores
- pHI
- 0.219
- hipred
- N
- hipred_score
- 0.432
- ghis
- 0.428
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.895
Gene Damage Prediction
All | Recessive | Dominant | |
---|---|---|---|
Mendelian | Medium | Medium | Medium |
Primary Immunodeficiency | Medium | Medium | Medium |
Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- C2
- Phenotype
Gene ontology
- Biological process
- proteolysis;complement activation;complement activation, classical pathway;response to nutrient;regulation of complement activation;innate immune response;positive regulation of apoptotic cell clearance
- Cellular component
- extracellular region;extracellular space;extracellular exosome
- Molecular function
- serine-type endopeptidase activity;protein binding;metal ion binding