DYSF
dysferlin, the group of Ferlin family
Basic information
Region (hg38): 2:71453561-71686763
Previous symbols: [ "LGMD2B" ]
Links
Phenotypes
GenCC
Source:
- neuromuscular disease caused by qualitative or quantitative defects of dysferlin (Definitive), mode of inheritance: AR
- autosomal recessive limb-girdle muscular dystrophy type 2B (Supportive), mode of inheritance: AR
- Miyoshi myopathy (Supportive), mode of inheritance: AR
- congenital myopathy, Paradas type (Supportive), mode of inheritance: AR
- distal myopathy with anterior tibial onset (Strong), mode of inheritance: AR
- autosomal recessive limb-girdle muscular dystrophy type 2B (Strong), mode of inheritance: AR
- autosomal recessive limb-girdle muscular dystrophy (Definitive), mode of inheritance: AR
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Miyoshi muscular dystrophy 1; Muscular dystrophy, limb-girdle, autosomal recessive, 2; Myopathy, distal, with anterior tibial onset | AR | Cardiovascular | Individuals may have mild cardiac anomalies, as well as more severe cardiac manifestations such as dilated cardiomyopathy, and surveillance (eg, with echocardiogram) may allow early detection and management of sequelae | Cardiovascular; Musculoskeletal | 3942856; 9009996; 8808603; 9731527; 9731526; 10196377; 10469840; 11134403; 10766988; 11198284; 16087766; 17287450; 17994539; 18306167; 19084402; 20535123; 21522182; 22297152; 22517428; 21816046 |
ClinVar
This is a list of variants' phenotypes submitted to
- Neuromuscular_disease_caused_by_qualitative_or_quantitative_defects_of_dysferlin (3222 variants)
- not_provided (1221 variants)
- Autosomal_recessive_limb-girdle_muscular_dystrophy_type_2B (1096 variants)
- Miyoshi_muscular_dystrophy_1 (499 variants)
- Distal_myopathy_with_anterior_tibial_onset (280 variants)
- Inborn_genetic_diseases (243 variants)
- not_specified (183 variants)
- Autosomal_recessive_limb-girdle_muscular_dystrophy (147 variants)
- DYSF-related_disorder (99 variants)
- Miyoshi_myopathy (79 variants)
- Limb-girdle_muscular_dystrophy,_recessive (76 variants)
- Abnormality_of_the_musculature (12 variants)
- Muscular_dystrophy (3 variants)
- Distal_lower_limb_muscle_weakness (2 variants)
- See_cases (2 variants)
- EMG:_myopathic_abnormalities (1 variants)
- Peripheral_neuropathy (1 variants)
- Arthralgia (1 variants)
- Schizophrenia (1 variants)
- Peroneal_muscle_atrophy (1 variants)
- Primary_dilated_cardiomyopathy (1 variants)
- Muscle_weakness (1 variants)
- Foot_dorsiflexor_weakness (1 variants)
- Proximal_muscle_weakness (1 variants)
- Myalgia (1 variants)
- Absent_muscle_fiber_dysferlin (1 variants)
- Myopathy (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the DYSF gene is commonly pathogenic or not. These statistics are base on transcript: NM_001130987.2. 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 | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 47 | 1023 | 1079 | |||
| missense | 41 | 113 | 968 | 200 | 13 | 1335 |
| nonsense | 123 | 91 | 214 | |||
| start loss | 0 | |||||
| frameshift | 193 | 133 | 329 | |||
| splice donor/acceptor (+/-2bp) | 70 | 109 | 185 | |||
| Total | 427 | 450 | 1021 | 1226 | 18 |
Highest pathogenic variant AF is 0.00020570956
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| DYSF | protein_coding | protein_coding | ENST00000410020 | 56 | 233047 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 3.65e-33 | 1.00 | 125477 | 0 | 271 | 125748 | 0.00108 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 0.0389 | 1232 | 1.24e+3 | 0.997 | 0.0000834 | 13861 |
| Missense in Polyphen | 433 | 437.06 | 0.99071 | 4677 | ||
| Synonymous | -1.86 | 551 | 498 | 1.11 | 0.0000338 | 4112 |
| Loss of Function | 4.01 | 72 | 119 | 0.603 | 0.00000616 | 1350 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00446 | 0.00440 |
| Ashkenazi Jewish | 0.0000994 | 0.0000992 |
| East Asian | 0.00174 | 0.00174 |
| Finnish | 0.000140 | 0.000139 |
| European (Non-Finnish) | 0.000854 | 0.000853 |
| Middle Eastern | 0.00174 | 0.00174 |
| South Asian | 0.00112 | 0.00111 |
| Other | 0.000816 | 0.000815 |
dbNSFP
Source:
- Function
- FUNCTION: Key calcium ion sensor involved in the Ca(2+)-triggered synaptic vesicle-plasma membrane fusion. Plays a role in the sarcolemma repair mechanism of both skeletal muscle and cardiomyocytes that permits rapid resealing of membranes disrupted by mechanical stress (By similarity). {ECO:0000250}.;
- Disease
- DISEASE: Limb-girdle muscular dystrophy 2B (LGMD2B) [MIM:253601]: An autosomal recessive degenerative myopathy characterized by weakness and atrophy starting in the proximal pelvifemoral muscles, with onset in the late teens or later, massive elevation of serum creatine kinase levels and slow progression. Scapular muscle involvement is minor and not present at onset. Upper limb girdle involvement follows some years after the onset in lower limbs. {ECO:0000269|PubMed:10196377, ECO:0000269|PubMed:11134403, ECO:0000269|PubMed:14678801, ECO:0000269|PubMed:15469449, ECO:0000269|PubMed:16010686, ECO:0000269|PubMed:16100712, ECO:0000269|PubMed:16705711, ECO:0000269|PubMed:16996541, ECO:0000269|PubMed:17185750, ECO:0000269|PubMed:17287450, ECO:0000269|PubMed:18306167, ECO:0000269|PubMed:18853459, ECO:0000269|PubMed:9731526}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Miyoshi muscular dystrophy 1 (MMD1) [MIM:254130]: A late- onset muscular dystrophy involving the distal lower limb musculature. It is characterized by weakness that initially affects the gastrocnemius muscle during early adulthood. {ECO:0000269|PubMed:10196377, ECO:0000269|PubMed:11134403, ECO:0000269|PubMed:11468312, ECO:0000269|PubMed:11959863, ECO:0000269|PubMed:12796534, ECO:0000269|PubMed:15116377, ECO:0000269|PubMed:15469449, ECO:0000269|PubMed:15477515, ECO:0000269|PubMed:15515206, ECO:0000269|PubMed:16010686, ECO:0000269|PubMed:16100712, ECO:0000269|PubMed:17287450, ECO:0000269|PubMed:18306167, ECO:0000269|PubMed:18853459, ECO:0000269|PubMed:9731526, ECO:0000269|Ref.27}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Distal myopathy with anterior tibial onset (DMAT) [MIM:606768]: Onset of the disorder is between 14 and 28 years of age and the anterior tibial muscles are the first muscle group to be involved. Inheritance is autosomal recessive. {ECO:0000269|PubMed:11198284}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Smooth Muscle Contraction;Muscle contraction
(Consensus)
Recessive Scores
- pRec
- 0.307
Intolerance Scores
- loftool
- 0.00220
- rvis_EVS
- -1.31
- rvis_percentile_EVS
- 4.85
Haploinsufficiency Scores
- pHI
- 0.187
- hipred
- Y
- hipred_score
- 0.683
- ghis
- 0.507
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.776
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Dysf
- Phenotype
- muscle phenotype; immune system phenotype; homeostasis/metabolism phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan);
Zebrafish Information Network
- Gene name
- dysf
- Affected structure
- muscle
- Phenotype tag
- abnormal
- Phenotype quality
- refractivity
Gene ontology
- Biological process
- angiogenesis;plasma membrane repair;positive regulation of endothelial cell proliferation;monocyte activation involved in immune response;macrophage activation involved in immune response;glycerol metabolic process;vesicle fusion;muscle contraction;negative regulation of gene expression;lipid storage;T-tubule organization;negative regulation of protein catabolic process;skeletal muscle tissue regeneration;fat cell differentiation;positive regulation of cell adhesion;muscle fiber development;cytokine secretion;negative regulation of phagocytosis;cellular response to osmotic stress;positive regulation of neutrophil chemotaxis;regulation of calcium ion import;negative regulation of high voltage-gated calcium channel activity;negative regulation of protein polyubiquitination
- Cellular component
- nucleus;endosome;early endosome;late endosome;Golgi apparatus;microtubule organizing center;microtubule;plasma membrane;integral component of membrane;lamellipodium;endocytic vesicle;T-tubule;cytoplasmic vesicle membrane;sarcolemma;extracellular exosome;membrane microdomain
- Molecular function
- calcium ion binding;protein binding;phospholipid binding;calcium-dependent phospholipid binding;microtubule binding;alpha-tubulin binding