CAP2

cyclase associated actin cytoskeleton regulatory protein 2

Basic information

Region (hg38): 6:17393594-17557780

Links

ENSG00000112186 ∙ NCBI:10486 ∙ OMIM:618385 ∙ HGNC:20039 ∙ Uniprot:P40123 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• familial isolated dilated cardiomyopathy (Supportive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cardiomyopathy, dilated, 2I	AR	Cardiovascular	The condition can involve structural cardiac anomalies, arrhthymias, and congestive heart failure, and awanress may be beneficial realed to medical management; Cardiac transplant has been described	Cardiovascular; Musculoskeletal	30518548; 33083013; 34862840

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CAP2 gene.

• Inborn genetic diseases (16 variants)
• not provided (6 variants)
• Cardiomyopathy, dilated, 2I (1 variants)
• CAP2-associated dilated cardiomyopathy (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CAP2 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					1	1
missense			19	2		21
nonsense						0
start loss			1			1
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			1			1
non coding						0
Total	0	0	20	2	1

Variants in CAP2

This is a list of pathogenic ClinVar variants found in the CAP2 region.

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

Position	Type	Phenotype	Significance	ClinVar
6-17421557-T-C		Cardiomyopathy, dilated, 2I	Uncertain significance (Nov 07, 2021)
6-17421593-G-A		Cardiomyopathy, dilated, 2I	Uncertain significance (Jun 07, 2021)
6-17421605-G-A		not specified • Cardiomyopathy, dilated, 2I	Uncertain significance (Nov 28, 2023)
6-17421614-C-T		not specified	Likely benign (Aug 21, 2023)
6-17421641-C-A		CAP2-associated dilated cardiomyopathy	Uncertain significance (May 21, 2021)
6-17421665-G-A		not specified	Uncertain significance (Jan 03, 2024)
6-17426592-G-A		not specified	Uncertain significance (Dec 07, 2023)
6-17426623-T-C			Uncertain significance (Sep 09, 2022)
6-17426627-G-A		not specified	Uncertain significance (Feb 17, 2024)
6-17426679-G-T		not specified	Uncertain significance (Nov 03, 2022)
6-17507218-T-A		not specified	Uncertain significance (Dec 01, 2022)
6-17507241-C-T		not specified	Uncertain significance (Apr 25, 2023)
6-17507269-C-T		not specified	Uncertain significance (Apr 22, 2022)
6-17507274-G-A			Uncertain significance (Mar 11, 2022)
6-17507310-G-C		not specified	Uncertain significance (Mar 23, 2022)
6-17507311-T-C		not specified	Uncertain significance (May 17, 2023)
6-17507680-G-A		not specified	Uncertain significance (Nov 18, 2022)
6-17507704-G-A		not specified	Uncertain significance (Dec 13, 2022)
6-17513926-A-G			Uncertain significance (Sep 09, 2022)
6-17513932-C-T		not specified	Uncertain significance (Jan 23, 2024)
6-17539287-G-A		not specified	Uncertain significance (Mar 11, 2022)
6-17539383-G-A		not specified	Uncertain significance (Jan 16, 2024)
6-17539410-C-T		not specified	Uncertain significance (Dec 14, 2021)
6-17540978-C-T		not specified	Uncertain significance (Jun 29, 2023)
6-17541092-T-C		not specified	Likely benign (Oct 05, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CAP2	protein_coding	protein_coding	ENST00000229922	12	164577

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.699	0.301	125733	0	13	125746	0.0000517

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.10	221	272	0.812	0.0000145	3141
Missense in Polyphen		77	119.43	0.64474		1408
Synonymous	0.532	93	99.8	0.932	0.00000589	906
Loss of Function	3.80	5	25.9	0.193	0.00000119	305

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000123	0.000123
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000887	0.0000879
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May have a regulatory bifunctional role.
• Pathway: Ectoderm Differentiation;Aryl Hydrocarbon Receptor Pathway;Nuclear Receptors Meta-Pathway;Developmental Biology;Signaling by ROBO receptors;Axon guidance;Role of ABL in ROBO-SLIT signaling (Consensus)

Recessive Scores

• pRec: 0.105

Intolerance Scores

• loftool: 0.312
• rvis_EVS: -0.05
• rvis_percentile_EVS: 50.22

Haploinsufficiency Scores

• pHI: 0.323
• hipred: Y
• hipred_score: 0.500
• ghis: 0.524

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.0194

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Cap2
• 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); 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); immune system phenotype; vision/eye phenotype; muscle phenotype; limbs/digits/tail phenotype; growth/size/body region phenotype; homeostasis/metabolism phenotype

Zebrafish Information Network

• Gene name: cap2
• Affected structure: whole organism
• Phenotype tag: abnormal
• Phenotype quality: decreased length

Gene ontology

• Biological process: cell morphogenesis;establishment or maintenance of cell polarity;signal transduction;activation of adenylate cyclase activity;actin polymerization or depolymerization
• Cellular component: plasma membrane;postsynaptic density;cortical actin cytoskeleton
• Molecular function: actin binding;protein binding;adenylate cyclase binding;identical protein binding