CR2

complement C3d receptor 2, the group of CD molecules|Sushi domain containing|Complement system regulators and receptors

Basic information

Region (hg38): 1:207453024-207489895

Links

ENSG00000117322 ∙ NCBI:1380 ∙ OMIM:120650 ∙ HGNC:2336 ∙ Uniprot:P20023 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• immunodeficiency, common variable, 7 (Moderate), mode of inheritance: AR
• common variable immunodeficiency (Supportive), mode of inheritance: AD
• immunodeficiency, common variable, 7 (Strong), mode of inheritance: AR
• immunodeficiency, common variable, 7 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Common variable immune deficiency, 7	AR	Allergy/Immunology/Infectious	Antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial	Allergy/Immunology/Infectious	22035880

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CR2 gene.

• Immunodeficiency, common variable, 7 (33 variants)
• not provided (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CR2 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			4	144	9	157
missense		2	339	18	7	366
nonsense	16	2	1			19
start loss						0
frameshift	16	4	2			22
inframe indel			3			3
splice donor/acceptor (+/-2bp)	2	6				8
splice region			14	17	3	34
non coding			5	62	25	92
Total	34	14	354	224	41

Highest pathogenic variant AF is 0.0000526

Variants in CR2

This is a list of pathogenic ClinVar variants found in the CR2 region.

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

Position	Type	Phenotype	Significance	ClinVar
1-207454348-T-C		Immunodeficiency, common variable, 7	Benign (Dec 22, 2023)
1-207454425-G-T		Immunodeficiency, common variable, 7	Uncertain significance (Nov 27, 2023)
1-207454427-C-T		Immunodeficiency, common variable, 7	Likely benign (Feb 01, 2024)
1-207454430-G-A		Immunodeficiency, common variable, 7	Likely benign (Dec 02, 2023)
1-207454439-C-T		Immunodeficiency, common variable, 7 • CR2-related disorder	Likely benign (Oct 23, 2023)
1-207454450-T-C		Immunodeficiency, common variable, 7	Uncertain significance (Oct 04, 2022)
1-207454457-C-G		Immunodeficiency, common variable, 7	Likely benign (Dec 26, 2023)
1-207454457-C-CG		Immunodeficiency, common variable, 7	Pathogenic (Dec 31, 2022)
1-207454458-G-C		Immunodeficiency, common variable, 7	Uncertain significance (Nov 14, 2019)
1-207454460-C-T		Immunodeficiency, common variable, 7	Likely benign (Apr 22, 2023)
1-207454470-G-A		Immunodeficiency, common variable, 7	Uncertain significance (Nov 27, 2018)
1-207454472-C-T		Immunodeficiency, common variable, 7	Likely benign (Mar 15, 2022)
1-207454488-G-C		Immunodeficiency, common variable, 7	Likely benign (Jun 19, 2021)
1-207454489-G-A		Immunodeficiency, common variable, 7	Benign (Jan 25, 2024)
1-207454489-G-T		Immunodeficiency, common variable, 7	Likely benign (Sep 28, 2022)
1-207454495-C-T		Immunodeficiency, common variable, 7	Uncertain significance (Nov 27, 2021)
1-207454573-G-A		Immunodeficiency, common variable, 7	Benign (Jan 19, 2024)
1-207466350-C-G			Benign (Nov 10, 2018)
1-207466506-G-A		Immunodeficiency, common variable, 7	Likely benign (Nov 23, 2022)
1-207466509-C-T		Immunodeficiency, common variable, 7	Likely benign (Jul 19, 2023)
1-207466513-T-C		Immunodeficiency, common variable, 7	Likely benign (May 24, 2022)
1-207466514-T-G		Immunodeficiency, common variable, 7	Likely benign (Jun 20, 2022)
1-207466516-T-C		Immunodeficiency, common variable, 7	Likely benign (Dec 28, 2023)
1-207466518-C-T		Immunodeficiency, common variable, 7	Likely benign (Nov 10, 2020)
1-207466521-T-C		Immunodeficiency, common variable, 7	Uncertain significance (May 12, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CR2	protein_coding	protein_coding	ENST00000367057	19	35666

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
4.74e-19	0.878	125652	0	94	125746	0.000374

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.793	542	597	0.909	0.0000315	7113
Missense in Polyphen		155	192.61	0.80474		2351
Synonymous	-0.549	221	211	1.05	0.0000112	2151
Loss of Function	2.29	38	56.6	0.671	0.00000334	660

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000513	0.000510
Ashkenazi Jewish	0.0000997	0.0000992
East Asian	0.00141	0.00141
Finnish	0.00	0.00
European (Non-Finnish)	0.000405	0.000404
Middle Eastern	0.00141	0.00141
South Asian	0.000229	0.000229
Other	0.000328	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Receptor for complement C3Dd, for the Epstein-Barr virus on human B-cells and T-cells and for HNRNPU (PubMed:7753047). Participates in B lymphocytes activation (PubMed:7753047). {ECO:0000269|PubMed:7753047}.
• Disease: DISEASE: Immunodeficiency, common variable, 7 (CVID7) [MIM:614699]: A primary immunodeficiency characterized by antibody deficiency, hypogammaglobulinemia, recurrent bacterial infections and an inability to mount an antibody response to antigen. The defect results from a failure of B-cell differentiation and impaired secretion of immunoglobulins; the numbers of circulating B-cells is usually in the normal range, but can be low. {ECO:0000269|PubMed:22035880}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Complement and coagulation cascades - Homo sapiens (human);B cell receptor signaling pathway - Homo sapiens (human);Hematopoietic cell lineage - Homo sapiens (human);Epstein-Barr virus infection - Homo sapiens (human);B Cell Receptor Signaling Pathway;Human Complement System;Dengue-2 Interactions with Complement and Coagulation Cascades;Oxidative Damage;Complement and Coagulation Cascades;Innate Immune System;Immune System;BCR;Regulation of Complement cascade;Complement cascade (Consensus)

Recessive Scores

• pRec: 0.458

Intolerance Scores

• loftool: 0.952
• rvis_EVS: 0.06
• rvis_percentile_EVS: 57.56

Haploinsufficiency Scores

• pHI: 0.134
• hipred: N
• hipred_score: 0.291

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.558

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High

Mouse Genome Informatics

• Gene name: Cr2
• Phenotype: homeostasis/metabolism phenotype; immune system 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); hematopoietic system phenotype

Gene ontology

• Biological process: complement receptor mediated signaling pathway;immune response;complement activation, classical pathway;B cell differentiation;regulation of complement activation;B cell proliferation;innate immune response;viral entry into host cell
• Cellular component: plasma membrane;integral component of membrane;receptor complex;extracellular exosome
• Molecular function: virus receptor activity;complement binding;DNA binding;complement receptor activity;transmembrane signaling receptor activity;protein binding;protein homodimerization activity