DYSF

dysferlin, the group of Ferlin family

Basic information

Region (hg38): 2:71453560-71686763

Previous symbols: [ "LGMD2B" ]

Links

ENSG00000135636 ∙ NCBI:8291 ∙ OMIM:603009 ∙ HGNC:3097 ∙ Uniprot:O75923 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• 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: CGD

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 ClinVar and linked to the DYSF gene.

• Qualitative or quantitative defects of dysferlin (2748 variants)
• not provided (1264 variants)
• Autosomal recessive limb-girdle muscular dystrophy type 2B (752 variants)
• Miyoshi muscular dystrophy 1 (319 variants)
• not specified (208 variants)
• Limb-Girdle Muscular Dystrophy, Recessive (103 variants)
• Miyoshi myopathy (103 variants)
• Inborn genetic diseases (76 variants)
• Distal myopathy with anterior tibial onset;Autosomal recessive limb-girdle muscular dystrophy type 2B;Miyoshi muscular dystrophy 1 (62 variants)
• Distal myopathy with anterior tibial onset;Miyoshi muscular dystrophy 1;Autosomal recessive limb-girdle muscular dystrophy type 2B (54 variants)
• Distal myopathy with anterior tibial onset (48 variants)
• Miyoshi muscular dystrophy 1;Autosomal recessive limb-girdle muscular dystrophy type 2B;Distal myopathy with anterior tibial onset (32 variants)
• Autosomal recessive limb-girdle muscular dystrophy (27 variants)
• Abnormality of the musculature (15 variants)
• DYSF-related condition (9 variants)
• DYSF-Related Disorders (7 variants)
• Autosomal recessive limb-girdle muscular dystrophy type 2B;Miyoshi muscular dystrophy 1;Distal myopathy with anterior tibial onset (4 variants)
• Muscular dystrophy (3 variants)
• Miyoshi muscular dystrophy 1;Distal myopathy with anterior tibial onset;Autosomal recessive limb-girdle muscular dystrophy type 2B (3 variants)
• See cases (2 variants)
• - (2 variants)
• Distal lower limb muscle weakness (1 variants)
• Absent muscle fiber dysferlin;Foot dorsiflexor weakness;Peroneal muscle atrophy;Distal lower limb muscle weakness (1 variants)
• Proximal muscle weakness (1 variants)
• Peripheral neuropathy (1 variants)
• Distal myopathy with anterior tibial onset;Autosomal recessive limb-girdle muscular dystrophy type 2B;Miyoshi myopathy;Qualitative or quantitative defects of dysferlin (1 variants)
• Muscle weakness;Myalgia;EMG: myopathic abnormalities;Arthralgia (1 variants)
• Autosomal recessive limb-girdle muscular dystrophy type 2B;Distal myopathy with anterior tibial onset;Miyoshi myopathy (1 variants)
• Primary dilated cardiomyopathy (1 variants)
• Miyoshi myopathy;Autosomal recessive limb-girdle muscular dystrophy type 2B;Qualitative or quantitative defects of dysferlin;Distal myopathy with anterior tibial onset (1 variants)
• DYSF- Related Disorder (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.

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			20	723	7	750
missense	16	51	760	65	5	897
nonsense	111	82				193
start loss		2				2
frameshift	151	100	2	2		255
inframe indel	1	1	27	2		31
splice donor/acceptor (+/-2bp)	57	87	4		1	149
splice region	4	8	53	156	1	222
non coding	3	1	31	436	148	619
Total	339	324	844	1228	161

Highest pathogenic variant AF is 0.0000526

Variants in DYSF

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

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

Position	Type	Phenotype	Significance	ClinVar
2-71453672-G-T		Qualitative or quantitative defects of dysferlin	Conflicting classifications of pathogenicity (Nov 01, 2022)
2-71453721-G-C		Qualitative or quantitative defects of dysferlin	Uncertain significance (Jan 12, 2018)
2-71453725-T-G		Qualitative or quantitative defects of dysferlin	Uncertain significance (Jan 12, 2018)
2-71453760-C-G		Qualitative or quantitative defects of dysferlin	Uncertain significance (Jan 13, 2018)
2-71453790-G-A			Likely benign (Nov 27, 2018)
2-71453820-C-A		Qualitative or quantitative defects of dysferlin	Benign (Jun 19, 2018)
2-71453949-T-A		not specified	Likely benign (Jul 19, 2017)
2-71453955-C-T		not specified	Likely benign (Mar 20, 2017)
2-71453965-G-T		not specified	Benign (Nov 07, 2017)
2-71453987-C-G		not specified	Likely benign (Aug 17, 2017)
2-71453992-G-A			Uncertain significance (Dec 22, 2017)
2-71453999-A-G		Autosomal recessive limb-girdle muscular dystrophy type 2B	Likely pathogenic (Dec 07, 2017)
2-71454000-T-C		Autosomal recessive limb-girdle muscular dystrophy type 2B • Qualitative or quantitative defects of dysferlin	Pathogenic/Likely pathogenic (Nov 12, 2023)
2-71454002-C-T		not specified • Qualitative or quantitative defects of dysferlin	Conflicting classifications of pathogenicity (Jan 04, 2024)
2-71454006-G-A			Uncertain significance (Jun 22, 2016)
2-71454007-G-A		Qualitative or quantitative defects of dysferlin	Likely benign (Oct 12, 2021)
2-71454007-G-C		Qualitative or quantitative defects of dysferlin	Uncertain significance (Apr 22, 2022)
2-71454009-T-G		Qualitative or quantitative defects of dysferlin	Uncertain significance (Jul 14, 2022)
2-71454015-T-A		Autosomal recessive limb-girdle muscular dystrophy type 2B • Qualitative or quantitative defects of dysferlin	Uncertain significance (Jul 18, 2022)
2-71454016-C-T		Qualitative or quantitative defects of dysferlin	Likely benign (Aug 08, 2022)
2-71454017-C-T		Qualitative or quantitative defects of dysferlin	Uncertain significance (Sep 06, 2022)
2-71454019-C-T		Qualitative or quantitative defects of dysferlin	Likely benign (Aug 30, 2023)
2-71454022-T-G		Qualitative or quantitative defects of dysferlin • Miyoshi muscular dystrophy 1	Pathogenic/Likely pathogenic (Nov 28, 2022)
2-71454023-G-A		Qualitative or quantitative defects of dysferlin	Uncertain significance (Aug 09, 2023)
2-71454025-C-G		Qualitative or quantitative defects of dysferlin • Autosomal recessive limb-girdle muscular dystrophy type 2B	Likely benign (Jan 25, 2024)

GnomAD

Source: gnomAD

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: dbNSFP

• 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