SGCA

sarcoglycan alpha

Basic information

Region (hg38): 17:50164214-50175928

Previous symbols: [ "ADL" ]

Links

ENSG00000108823 ∙ NCBI:6442 ∙ OMIM:600119 ∙ HGNC:10805 ∙ Uniprot:Q16586 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal recessive limb-girdle muscular dystrophy type 2D (Definitive), mode of inheritance: AR
• autosomal recessive limb-girdle muscular dystrophy type 2D (Strong), mode of inheritance: AR
• autosomal recessive limb-girdle muscular dystrophy type 2D (Definitive), mode of inheritance: AR
• autosomal recessive limb-girdle muscular dystrophy type 2D (Supportive), 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
Muscular dystrophy, limb-girdle, autosomal recessive 3	AR	Cardiovascular	The condition can include severe cardiac manifestations, and knowledge may allow surveillance (eg, with EKG, echocardiogram, and Holter monitoring) and early medical management, which may ameliorate morbidity and mortality; Heart transplantation may be indicated in individuals with severe dilated cardiomyopathy	Cardiovascular; Musculoskeletal	8069911; 7987694; 8528203; 7663524; 9032047; 18285821; 20627570

ClinVar

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

• Autosomal recessive limb-girdle muscular dystrophy type 2D (35 variants)
• not provided (16 variants)
• Abnormality of the musculature (3 variants)
• Autosomal recessive limb-girdle muscular dystrophy (2 variants)
• Sarcoglycanopathy (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SGCA 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			3	173	2	178
missense	6	34	154	1	1	196
nonsense	6	12				18
start loss		2				2
frameshift	25	38				63
inframe indel			6			6
splice donor/acceptor (+/-2bp)	4	20	1			25
splice region		4	13	24	1	42
non coding			9	98	26	133
Total	41	106	173	272	29

Highest pathogenic variant AF is 0.000433

Variants in SGCA

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

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

Position	Type	Phenotype	Significance	ClinVar
17-50165951-C-A			Benign/Likely benign (Jul 01, 2023)
17-50166010-T-C		Sarcoglycanopathy • not specified	Conflicting classifications of pathogenicity (Jan 13, 2018)
17-50166013-C-T		Sarcoglycanopathy	Uncertain significance (Jan 13, 2018)
17-50166018-C-T		not specified	Likely benign (Sep 23, 2016)
17-50166022-C-T		Sarcoglycanopathy	Uncertain significance (Mar 16, 2018)
17-50166023-G-A		Sarcoglycanopathy	Uncertain significance (Jan 13, 2018)
17-50166032-C-T		SGCA-related disorder	Likely benign (Sep 01, 2023)
17-50166033-G-A		Sarcoglycanopathy • not specified • Dystrophin deficiency • Autosomal recessive limb-girdle muscular dystrophy type 2D • SGCA-related disorder	Benign (Feb 08, 2023)
17-50166036-C-G		Sarcoglycanopathy • Autosomal recessive limb-girdle muscular dystrophy type 2D	Uncertain significance (Feb 08, 2023)
17-50166039-CCATGGCTGAG-C		Autosomal recessive limb-girdle muscular dystrophy type 2D	Likely pathogenic (Aug 02, 2016)
17-50166041-A-G		Autosomal recessive limb-girdle muscular dystrophy • Autosomal recessive limb-girdle muscular dystrophy type 2D	Pathogenic/Likely pathogenic (Mar 20, 2023)
17-50166053-C-G		Autosomal recessive limb-girdle muscular dystrophy type 2D	Uncertain significance (Apr 27, 2023)
17-50166058-C-T		Autosomal recessive limb-girdle muscular dystrophy type 2D	Likely benign (Dec 20, 2022)
17-50166060-G-A		Autosomal recessive limb-girdle muscular dystrophy type 2D	Likely pathogenic (Dec 06, 2022)
17-50166062-ACTCCT-A		Autosomal recessive limb-girdle muscular dystrophy type 2D	Pathogenic (Dec 16, 2022)
17-50166064-T-TC		Autosomal recessive limb-girdle muscular dystrophy type 2D	Pathogenic (Jan 06, 2023)
17-50166068-C-T		Autosomal recessive limb-girdle muscular dystrophy type 2D	Uncertain significance (Jun 01, 2023)
17-50166070-C-G		Autosomal recessive limb-girdle muscular dystrophy type 2D	Likely benign (Oct 30, 2023)
17-50166073-C-T		Autosomal recessive limb-girdle muscular dystrophy type 2D	Conflicting classifications of pathogenicity (Oct 13, 2023)
17-50166074-G-A		Autosomal recessive limb-girdle muscular dystrophy type 2D	Conflicting classifications of pathogenicity (Dec 22, 2023)
17-50166077-G-A		Autosomal recessive limb-girdle muscular dystrophy type 2D	Uncertain significance (Feb 12, 2022)
17-50166078-G-A		Autosomal recessive limb-girdle muscular dystrophy type 2D	Likely pathogenic (-)
17-50166078-G-C		Autosomal recessive limb-girdle muscular dystrophy type 2D	Likely pathogenic (Jul 07, 2020)
17-50166078-G-T		Autosomal recessive limb-girdle muscular dystrophy type 2D	Likely pathogenic (Jan 03, 2024)
17-50166079-C-G		Autosomal recessive limb-girdle muscular dystrophy type 2D	Pathogenic/Likely pathogenic (Jun 22, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SGCA	protein_coding	protein_coding	ENST00000262018	9	11718

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00271	0.985	125721	0	27	125748	0.000107

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.676	214	244	0.878	0.0000162	2445
Missense in Polyphen		68	85.262	0.79754		880
Synonymous	0.108	99	100	0.986	0.00000648	836
Loss of Function	2.19	7	16.7	0.420	8.08e-7	181

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000217	0.000213
Ashkenazi Jewish	0.00	0.00
East Asian	0.000218	0.000217
Finnish	0.00	0.00
European (Non-Finnish)	0.000158	0.000158
Middle Eastern	0.000218	0.000217
South Asian	0.00	0.00
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Component of the sarcoglycan complex, a subcomplex of the dystrophin-glycoprotein complex which forms a link between the F-actin cytoskeleton and the extracellular matrix.
• Pathway: Dilated cardiomyopathy (DCM) - Homo sapiens (human);Viral myocarditis - Homo sapiens (human);Arrhythmogenic right ventricular cardiomyopathy (ARVC) - Homo sapiens (human);Hypertrophic cardiomyopathy (HCM) - Homo sapiens (human);Arrhythmogenic Right Ventricular Cardiomyopathy (Consensus)

Recessive Scores

• pRec: 0.103

Intolerance Scores

• loftool: 0.0528
• rvis_EVS: -0.71
• rvis_percentile_EVS: 14.5

Haploinsufficiency Scores

• pHI: 0.136
• hipred: Y
• hipred_score: 0.696
• ghis: 0.586

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.554

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Sgca
• Phenotype: homeostasis/metabolism phenotype; muscle phenotype; immune system phenotype; 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)

Gene ontology

• Biological process: muscle contraction;muscle organ development
• Cellular component: cytoplasm;cytoskeleton;cell-cell junction;dystrophin-associated glycoprotein complex;sarcoglycan complex;integral component of membrane;sarcolemma;membrane raft
• Molecular function: calcium ion binding;protein binding