CYFIP2

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

Basic information

Region (hg38): 5:157266078-157395595

Links

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

Phenotypes

GenCC

Source: genCC

• developmental and epileptic encephalopathy, 76 (Definitive), 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 (Strong), 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 (645 variants)
• Developmental and epileptic encephalopathy, 65 (44 variants)
• Inborn genetic diseases (34 variants)
• not specified (4 variants)
• Seizure (2 variants)
• Intellectual disability (1 variants)
• Global developmental delay (1 variants)
• CYFIP2-related condition (1 variants)
• Neurodevelopmental delay (1 variants)
• See cases (1 variants)
• CYFIP2-related neurodevelopmental disorders (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.

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	185	26	215
missense	4	15	197	26	2	244
nonsense			8			8
start loss						0
frameshift			3	1	1	5
inframe indel						0
splice donor/acceptor (+/-2bp)			3	1		4
splice region			25	25	7	57
non coding			43	85	26	154
Total	4	15	258	298	55

Highest pathogenic variant AF is 0.0000263

Variants in CYFIP2

This is a list of pathogenic ClinVar variants found in the CYFIP2 region.

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

Position	Type	Phenotype	Significance	ClinVar
5-157285369-C-T		Developmental and epileptic encephalopathy, 65	Conflicting classifications of pathogenicity (Jan 02, 2024)
5-157285370-G-A			Likely benign (Nov 30, 2022)
5-157285370-G-T			Likely benign (Jan 28, 2023)
5-157285373-C-T			Likely benign (Oct 18, 2023)
5-157285374-G-A			Likely benign (Aug 10, 2023)
5-157285380-C-T			Likely benign (Apr 15, 2023)
5-157285391-C-T			Likely benign (Dec 21, 2023)
5-157285400-C-T			Likely benign (Nov 27, 2023)
5-157285403-G-T			Likely benign (Dec 09, 2023)
5-157285409-G-C			Likely benign (Dec 13, 2023)
5-157285418-G-C		Inborn genetic diseases	Uncertain significance (Dec 28, 2022)
5-157285430-C-G			Likely benign (Oct 28, 2023)
5-157285430-C-T			Likely benign (May 25, 2023)
5-157285431-G-A			Uncertain significance (Mar 29, 2022)
5-157285442-A-G			Benign (Jan 24, 2024)
5-157285452-C-T			Uncertain significance (Jul 31, 2022)
5-157285467-A-G			Uncertain significance (Oct 25, 2022)
5-157285470-A-G			Uncertain significance (Jun 02, 2023)
5-157285472-G-A			Uncertain significance (Jun 27, 2022)
5-157285482-A-G			Likely benign (May 12, 2022)
5-157285487-A-C			Benign (Oct 15, 2022)
5-157285487-A-T			Likely benign (May 16, 2023)
5-157285490-G-A			Likely benign (Dec 29, 2020)
5-157285491-G-A			Likely benign (Sep 10, 2023)
5-157285493-A-G			Likely benign (Mar 29, 2023)

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
1.00	3.98e-10	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

Haploinsufficiency Scores

• pHI: 0.446
• hipred: Y
• hipred_score: 0.728
• ghis: 0.579

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

Mouse Genome Informatics

• Gene name: Cyfip2
• Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); 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); normal 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); renal/urinary system phenotype; homeostasis/metabolism phenotype

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