CYFIP2

cytoplasmic FMR1 interacting protein 2, the group of SCAR/WAVE complex

Basic information

Region (hg38): 5:157266079-157395595

Links

ENSG00000055163 ∙ NCBI:26999 ∙ OMIM:606323 ∙ HGNC:13760 ∙ Uniprot:Q96F07 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Transcripts

Transcript IDs starting with ENST are treated as Ensembl, all others as RefSeq. Showing 4 of 49.

Transcript ID	Protein ID	Coding exons	MANE Select	MANE Plus Clinical
ENST00000435847.6	ENSP00000403793.3	27	-	-
ENST00000520960.2	ENSP00000482739.1	3	-	-
ENST00000521420.5	ENSP00000430904.1	29	-	-
ENST00000522463.5	ENSP00000428009.1	25	-	-

Phenotypes

GenCC

Source: genCC

• complex neurodevelopmental disorder (Definitive), mode of inheritance: AD
• developmental and epileptic encephalopathy, 65 (Strong), mode of inheritance: AD
• developmental and epileptic encephalopathy, 65 (Strong), mode of inheritance: AD
• undetermined early-onset epileptic encephalopathy (Supportive), mode of inheritance: AD
• developmental and epileptic encephalopathy, 65 (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Developmental and epileptic encephalopathy 65	AD	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	Craniofacial; Neurologic	29534297

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CYFIP2 gene.

• not_provided (1031 variants)
• Inborn_genetic_diseases (69 variants)
• Developmental_and_epileptic_encephalopathy,_65 (59 variants)
• not_specified (44 variants)
• CYFIP2-related_disorder (20 variants)
• Seizure (3 variants)
• See_cases (2 variants)
• CYFIP2-related_neurodevelopmental_disorders (1 variants)
• Global_developmental_delay (1 variants)
• Intellectual_disability (1 variants)
• Complex_neurodevelopmental_disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CYFIP2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001037333.3. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			4	286	23	313
missense	5	19	345	77	2	448
nonsense			16	2		18
start loss						0
frameshift			6	1	1	8
splice donor/acceptor (+/-2bp)	1		12	2		15
Total	6	19	383	368	26

Highest pathogenic variant AF is 0.0000065690074

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CYFIP2	protein_coding	protein_coding	ENST00000521420	29	129518

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
		125632	0	3	125635	0.0000119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	6.01	274	732	0.374	0.0000442	8113
Missense in Polyphen		52	197.5	0.26329		2197
Synonymous	-0.160	292	289	1.01	0.0000185	2272
Loss of Function	7.43	2	68.2	0.0293	0.00000369	770

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000177	0.0000176
Middle Eastern	0.00	0.00
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in T-cell adhesion and p53/TP53-dependent induction of apoptosis. Does not bind RNA. As component of the WAVE1 complex, required for BDNF-NTRK2 endocytic trafficking and signaling from early endosomes (By similarity). {ECO:0000250|UniProtKB:Q5SQX6, ECO:0000269|PubMed:10449408, ECO:0000269|PubMed:15048733, ECO:0000269|PubMed:17245118}.
• Disease: DISEASE: Epileptic encephalopathy, early infantile, 65 (EIEE65) [MIM:618008]: A form of epileptic encephalopathy, a heterogeneous group of severe childhood onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. EIEE65 is an autosomal dominant form characterized by onset of intractable seizures usually in the first 6 months of life and severe to profound psychomotor developmental delay. {ECO:0000269|PubMed:29534297}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: RNA transport - Homo sapiens (human);Regulation of actin cytoskeleton - Homo sapiens (human);Regulation of Actin Cytoskeleton;Signal Transduction;VEGFA-VEGFR2 Pathway;Fcgamma receptor (FCGR) dependent phagocytosis;Innate Immune System;Immune System;RHO GTPases Activate WASPs and WAVEs;RHO GTPase Effectors;Signaling by Rho GTPases;ErbB1 downstream signaling;Regulation of actin dynamics for phagocytic cup formation;Signaling by VEGF;Signaling by Receptor Tyrosine Kinases;Stabilization and expansion of the E-cadherin adherens junction;RAC1 signaling pathway;PDGFR-beta signaling pathway;E-cadherin signaling in the nascent adherens junction (Consensus)

Recessive Scores

• pRec: 0.505

Essentials

• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.827

Gene Damage Prediction

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

Zebrafish Information Network

• Gene name: cyfip2
• Affected structure: retinal ganglion cell
• Phenotype tag: abnormal
• Phenotype quality: mislocalised

Gene ontology

• Biological process: cell morphogenesis;apoptotic process;axon guidance;cell projection assembly;Fc-gamma receptor signaling pathway involved in phagocytosis;positive regulation of proteolysis;vascular endothelial growth factor receptor signaling pathway;positive regulation of neurotrophin TRK receptor signaling pathway;activation of cysteine-type endopeptidase activity;dendrite extension;cell-cell adhesion
• Cellular component: nucleus;cytoplasm;cytosol;membrane;cell junction;SCAR complex;neuron projection;synapse;perinuclear region of cytoplasm;extracellular exosome
• Molecular function: RNA 7-methylguanosine cap binding;protein binding