CFL2

cofilin 2

Basic information

Region (hg38): 14:34709113-34714823

Links

ENSG00000165410 ∙ NCBI:1073 ∙ OMIM:601443 ∙ HGNC:1875 ∙ Uniprot:Q9Y281 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• nemaline myopathy 7 (Strong), mode of inheritance: AR
• nemaline myopathy 7 (Strong), mode of inheritance: AR
• nemaline myopathy 7 (Moderate), mode of inheritance: AR
• typical nemaline myopathy (Supportive), mode of inheritance: AD
• nemaline myopathy 7 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Nemaline myopathy 7	AR	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	Musculoskeletal	17160903

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CFL2 gene.

• Nemaline myopathy 7 (5 variants)
• CFL2-related disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CFL2 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			2	16		18
missense			43			43
nonsense		1				1
start loss	1		1			2
frameshift	3		1			4
inframe indel			4			4
splice donor/acceptor (+/-2bp)						0
splice region	1		1	2	2	6
non coding			24	21	15	60
Total	4	1	75	37	15

Highest pathogenic variant AF is 0.0000263

Variants in CFL2

This is a list of pathogenic ClinVar variants found in the CFL2 region.

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

Position	Type	Phenotype	Significance	ClinVar
14-34710525-A-C		Nemaline myopathy 7	Uncertain significance (Jan 13, 2018)
14-34710581-G-A		Nemaline myopathy 7	Uncertain significance (Jan 13, 2018)
14-34710617-C-T		Nemaline myopathy 7	Uncertain significance (Jan 12, 2018)
14-34710631-GA-G		Nemaline Myopathy, Recessive	Uncertain significance (Jun 14, 2016)
14-34710786-C-CAAG		Nemaline Myopathy, Recessive	Uncertain significance (Jun 14, 2016)
14-34710827-C-A		Nemaline myopathy 7	Benign (Jan 12, 2018)
14-34710960-T-C		Nemaline myopathy 7	Benign (Jan 12, 2018)
14-34710979-C-T		Nemaline myopathy 7	Uncertain significance (Jan 12, 2018)
14-34710980-G-A		Nemaline myopathy 7	Uncertain significance (Jan 12, 2018)
14-34711055-A-T		Nemaline myopathy 7	Uncertain significance (Jan 12, 2018)
14-34711106-T-C		Nemaline myopathy 7	Uncertain significance (Jan 13, 2018)
14-34711183-T-A		Nemaline myopathy 7	Benign (Jan 13, 2018)
14-34711245-A-G		Nemaline myopathy 7	Uncertain significance (Mar 30, 2018)
14-34711358-G-A		Nemaline myopathy 7	Uncertain significance (Jan 12, 2018)
14-34711471-AT-A		Nemaline Myopathy, Recessive	Benign (Jun 14, 2016)
14-34711567-AAAG-A		Nemaline Myopathy, Recessive	Benign (Jun 14, 2016)
14-34711597-G-A		Nemaline myopathy 7	Likely benign (Jan 13, 2018)
14-34711795-C-T		Nemaline myopathy 7	Uncertain significance (Jan 13, 2018)
14-34711829-C-T		Nemaline myopathy 7	Conflicting classifications of pathogenicity (Jul 01, 2023)
14-34711835-G-C		Nemaline myopathy 7	Uncertain significance (Jan 12, 2018)
14-34711870-A-G		Nemaline myopathy 7	Uncertain significance (Jan 13, 2018)
14-34711940-A-G		Nemaline myopathy 7	Benign (Jan 13, 2018)
14-34711960-T-C		Nemaline myopathy 7	Likely benign (Jan 13, 2018)
14-34712127-T-C		Nemaline myopathy 7	Uncertain significance (Jan 13, 2018)
14-34712145-T-A		Nemaline myopathy 7	Uncertain significance (Jan 13, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CFL2	protein_coding	protein_coding	ENST00000341223	4	4437

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000644	0.497	125723	0	17	125740	0.0000676

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.61	43	84.8	0.507	0.00000411	1090
Missense in Polyphen		6	15.462	0.38804		225
Synonymous	1.14	23	31.1	0.740	0.00000169	298
Loss of Function	0.472	7	8.48	0.825	4.44e-7	103

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000578	0.0000578
Ashkenazi Jewish	0.000198	0.000198
East Asian	0.000109	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.0000706	0.0000703
Middle Eastern	0.000109	0.000109
South Asian	0.0000980	0.0000980
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Controls reversibly actin polymerization and depolymerization in a pH-sensitive manner. Its F-actin depolymerization activity is regulated by association with CSPR3 (PubMed:19752190). It has the ability to bind G- and F-actin in a 1:1 ratio of cofilin to actin. It is the major component of intranuclear and cytoplasmic actin rods. Required for muscle maintenance. May play a role during the exchange of alpha-actin forms during the early postnatal remodeling of the sarcomere (By similarity). {ECO:0000250|UniProtKB:P45591, ECO:0000269|PubMed:19752190}.
• Disease: DISEASE: Nemaline myopathy 7 (NEM7) [MIM:610687]: A form of nemaline myopathy. Nemaline myopathies are muscular disorders characterized by muscle weakness of varying severity and onset, and abnormal thread-like or rod-shaped structures in muscle fibers on histologic examination. Nemaline myopathy type 7 presents at birth with hypotonia and generalized weakness. Major motor milestones are delayed, but independent ambulation is achieved. {ECO:0000269|PubMed:17160903, ECO:0000269|PubMed:22560515}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Fc gamma R-mediated phagocytosis - Homo sapiens (human);Pertussis - Homo sapiens (human);Regulation of actin cytoskeleton - Homo sapiens (human);Axon guidance - Homo sapiens (human);Leptin signaling pathway;Regulation of Microtubule Cytoskeleton;JAK-STAT;Regulation of Actin Cytoskeleton;G13 Signaling Pathway;Leptin;Caspase Cascade in Apoptosis (Consensus)

Recessive Scores

• pRec: 0.171

Intolerance Scores

• loftool: 0.563
• rvis_EVS: 0.01
• rvis_percentile_EVS: 54.63

Haploinsufficiency Scores

• pHI: 0.549
• hipred: Y
• hipred_score: 0.804
• ghis: 0.624

Essentials

• essential_gene_CRISPR: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.941

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Cfl2
• 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); muscle phenotype; growth/size/body region phenotype

Gene ontology

• Biological process: skeletal muscle tissue development;actin filament depolymerization;actin filament fragmentation;positive regulation of actin filament depolymerization;sarcomere organization;muscle cell cellular homeostasis
• Cellular component: extracellular space;actin cytoskeleton;nuclear matrix;Z disc;I band;extracellular exosome
• Molecular function: protein binding;actin filament binding