LIMS2

LIM zinc finger domain containing 2, the group of LIM zinc finger domain containing

Basic information

Region (hg38): 2:127638380-127681786

Links

ENSG00000072163 ∙ NCBI:55679 ∙ OMIM:607908 ∙ HGNC:16084 ∙ Uniprot:Q7Z4I7 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal recessive limb-girdle muscular dystrophy type 2W (Limited), mode of inheritance: AR
• autosomal recessive limb-girdle muscular dystrophy type 2W (Supportive), mode of inheritance: AR
• autosomal recessive limb-girdle muscular dystrophy type 2W (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Muscular dystrophy, autosomal recessive, with cardiomyopathy and triangular tongue	AD	Cardiovascular	The condition can include dilated cardiomyopathy, and knowledge may allow early diagnosis and medical management	Cardiovascular; Craniofacial; Musculoskeletal	25589244

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the LIMS2 gene.

• Autosomal recessive limb-girdle muscular dystrophy type 2W (231 variants)
• not provided (43 variants)
• Inborn genetic diseases (32 variants)
• not specified (7 variants)
• - (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the LIMS2 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			1	38	6	45
missense			102	1		103
nonsense			5			5
start loss			2			2
frameshift			3			3
inframe indel			3			3
splice donor/acceptor (+/-2bp)	1	1	2			4
splice region			5	11	2	18
non coding			25	38	37	100
Total	1	1	143	77	43

Variants in LIMS2

This is a list of pathogenic ClinVar variants found in the LIMS2 region.

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

Position	Type	Phenotype	Significance	ClinVar
2-127639232-A-G			Benign (Mar 06, 2021)
2-127639258-GAGGCAGCTGCGCAAGAGGGCCTTC-G		Autosomal recessive limb-girdle muscular dystrophy type 2W	Uncertain significance (Jan 22, 2023)
2-127639287-A-G		Autosomal recessive limb-girdle muscular dystrophy type 2W	Likely benign (Dec 14, 2022)
2-127639313-G-C		Autosomal recessive limb-girdle muscular dystrophy type 2W	Uncertain significance (Oct 18, 2022)
2-127639321-CG-C		Autosomal recessive limb-girdle muscular dystrophy type 2W	Uncertain significance (Feb 08, 2022)
2-127639322-G-A		Autosomal recessive limb-girdle muscular dystrophy type 2W	Uncertain significance (Jan 29, 2024)
2-127639325-A-G		Autosomal recessive limb-girdle muscular dystrophy type 2W	Uncertain significance (Nov 10, 2023)
2-127639326-G-T		Autosomal recessive limb-girdle muscular dystrophy type 2W	Likely benign (Dec 28, 2022)
2-127639336-G-A		Autosomal recessive limb-girdle muscular dystrophy type 2W	Uncertain significance (Dec 30, 2023)
2-127639337-A-ACAGCTTCTTCAG		Autosomal recessive limb-girdle muscular dystrophy type 2W	Uncertain significance (Jan 07, 2020)
2-127639339-A-G		Autosomal recessive limb-girdle muscular dystrophy type 2W	Pathogenic (Mar 22, 2021)
2-127639343-T-A		Autosomal recessive limb-girdle muscular dystrophy type 2W	Uncertain significance (Mar 14, 2024)
2-127639346-T-TA		Autosomal recessive limb-girdle muscular dystrophy type 2W	Uncertain significance (Dec 10, 2022)
2-127639352-G-A		Autosomal recessive limb-girdle muscular dystrophy type 2W	Uncertain significance (Sep 19, 2022)
2-127639361-G-A		Autosomal recessive limb-girdle muscular dystrophy type 2W	Likely benign (Feb 28, 2022)
2-127639367-G-T		Autosomal recessive limb-girdle muscular dystrophy type 2W	Uncertain significance (Nov 14, 2022)
2-127639368-C-T		Autosomal recessive limb-girdle muscular dystrophy type 2W	Likely benign (Dec 05, 2017)
2-127639379-C-T		Autosomal recessive limb-girdle muscular dystrophy type 2W	Uncertain significance (May 08, 2023)
2-127639380-G-A		Autosomal recessive limb-girdle muscular dystrophy type 2W	Likely benign (Jan 04, 2024)
2-127639380-G-C		Autosomal recessive limb-girdle muscular dystrophy type 2W	Uncertain significance (Jun 20, 2022)
2-127639398-G-A		Autosomal recessive limb-girdle muscular dystrophy type 2W	Likely benign (Aug 17, 2023)
2-127639407-G-A		Autosomal recessive limb-girdle muscular dystrophy type 2W	Likely benign (Jun 27, 2022)
2-127639409-C-G		Autosomal recessive limb-girdle muscular dystrophy type 2W	Uncertain significance (Jun 13, 2019)
2-127639409-C-T		Autosomal recessive limb-girdle muscular dystrophy type 2W	Uncertain significance (Aug 24, 2023)
2-127639410-G-A		Autosomal recessive limb-girdle muscular dystrophy type 2W	Likely benign (Nov 24, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
LIMS2	protein_coding	protein_coding	ENST00000324938	10	43405

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000505	0.970	125683	0	60	125743	0.000239

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.373	208	224	0.930	0.0000150	2387
Missense in Polyphen		96	95.424	1.006		963
Synonymous	1.15	81	95.2	0.850	0.00000701	664
Loss of Function	1.96	10	19.3	0.519	8.96e-7	235

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000709	0.000695
Ashkenazi Jewish	0.0000994	0.0000992
East Asian	0.000109	0.000109
Finnish	0.0000924	0.0000924
European (Non-Finnish)	0.000275	0.000273
Middle Eastern	0.000109	0.000109
South Asian	0.000236	0.000229
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Adapter protein in a cytoplasmic complex linking beta- integrins to the actin cytoskeleton, bridges the complex to cell surface receptor tyrosine kinases and growth factor receptors. Plays a role in modulating cell spreading and migration. {ECO:0000269|PubMed:12167643}.
• Disease: DISEASE: Limb-girdle muscular dystrophy 2W (LGMD2W) [MIM:616827]: A form of autosomal recessive limb-girdle muscular dystrophy, a degenerative myopathy characterized by slowly progressive wasting and weakness of the proximal muscles of arms and legs around the pelvic or shoulder girdles, elevated creatine kinase levels and dystrophic features on muscle biopsy. LGMD2W is characterized by childhood-onset of weakness progressing to a severe quadriparesis. Additionally, patients have biventricular cardiac dysfunction due to dilated cardiomyopathy. {ECO:0000269|PubMed:25589244}. Note=The disease may be caused by mutations affecting the gene represented in this entry.
• Pathway: Integrin-linked kinase signaling;Cell-extracellular matrix interactions;Cell junction organization;Cell-Cell communication (Consensus)

Recessive Scores

• pRec: 0.117

Intolerance Scores

• loftool: 0.0722
• rvis_EVS: -0.8
• rvis_percentile_EVS: 12.33

Haploinsufficiency Scores

• pHI: 0.401
• hipred: N
• hipred_score: 0.347
• ghis: 0.604

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.598

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Lims2
• Phenotype: respiratory system phenotype; liver/biliary system 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); normal 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); homeostasis/metabolism phenotype; growth/size/body region phenotype; muscle phenotype

Zebrafish Information Network

• Gene name: lims2
• Affected structure: pericardium
• Phenotype tag: abnormal
• Phenotype quality: edematous

Gene ontology

• Biological process: cell junction assembly;negative regulation of apoptotic process;cell-cell junction organization;cell-cell adhesion;negative regulation of neural precursor cell proliferation;negative regulation of hepatocyte proliferation;positive regulation of integrin-mediated signaling pathway
• Cellular component: nucleus;cytosol;plasma membrane;focal adhesion
• Molecular function: metal ion binding