LCA5

lebercilin LCA5

Basic information

Region (hg38): 6:79484990-79537458

Previous symbols: [ "C6orf152" ]

Links

ENSG00000135338 ∙ NCBI:167691 ∙ OMIM:611408 ∙ HGNC:31923 ∙ Uniprot:Q86VQ0 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Leber congenital amaurosis 5 (Definitive), mode of inheritance: AR
• Leber congenital amaurosis 5 (Strong), mode of inheritance: AR
• Leber congenital amaurosis (Supportive), mode of inheritance: AD
• severe early-childhood-onset retinal dystrophy (Supportive), mode of inheritance: AR
• Leber congenital amaurosis 5 (Definitive), mode of inheritance: AR
• LCA5-related retinopathy (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Leber congenital amaurosis 5	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	Ophthalmologic	10631161; 12642313; 17546029; 18334959; 20301475; 21850168

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the LCA5 gene.

• not provided (586 variants)
• Leber congenital amaurosis 5 (193 variants)
• Leber congenital amaurosis (44 variants)
• Inborn genetic diseases (34 variants)
• not specified (8 variants)
• Retinal dystrophy (8 variants)
• Retinitis pigmentosa (4 variants)
• Leber congenital amaurosis 1 (3 variants)
• LCA5-related condition (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the LCA5 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	204	5	211
missense		2	207	4	5	218
nonsense	30	8	1			39
start loss	2					2
frameshift	37	19	3			59
inframe indel			3			3
splice donor/acceptor (+/-2bp)	1	8				9
splice region			8	14	2	24
non coding			56	29	7	92
Total	70	37	272	237	17

Highest pathogenic variant AF is 0.0000657

Variants in LCA5

This is a list of pathogenic ClinVar variants found in the LCA5 region.

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

Position	Type	Phenotype	Significance	ClinVar
6-79485153-T-C		Leber congenital amaurosis 5	Uncertain significance (Jan 13, 2018)
6-79485227-A-T		Leber congenital amaurosis 5	Uncertain significance (Jan 13, 2018)
6-79485252-C-T		Leber congenital amaurosis 5	Uncertain significance (Jan 12, 2018)
6-79485324-G-T		Leber congenital amaurosis 5	Uncertain significance (Jan 12, 2018)
6-79485427-A-C		Leber congenital amaurosis 5	Uncertain significance (Jan 13, 2018)
6-79485431-T-C		Leber congenital amaurosis 5	Uncertain significance (Jan 12, 2018)
6-79485445-A-G		Leber congenital amaurosis 5	Uncertain significance (Jan 13, 2018)
6-79485461-A-G		Leber congenital amaurosis 5	Uncertain significance (Jan 12, 2018)
6-79485476-C-T		Leber congenital amaurosis 5	Likely benign (Jan 13, 2018)
6-79485509-C-T		Leber congenital amaurosis 5	Likely benign (Jan 13, 2018)
6-79485619-A-G		Leber congenital amaurosis 5	Uncertain significance (Jan 13, 2018)
6-79485678-T-C		Leber congenital amaurosis 5	Uncertain significance (Jan 13, 2018)
6-79485688-G-A		Leber congenital amaurosis 5	Uncertain significance (Jan 13, 2018)
6-79485704-C-T		Leber congenital amaurosis 5	Likely benign (Jan 13, 2018)
6-79485712-T-C		Leber congenital amaurosis 5	Benign (Apr 27, 2017)
6-79485743-T-C		Leber congenital amaurosis 5	Uncertain significance (Jan 13, 2018)
6-79485770-T-G		Leber congenital amaurosis 5	Uncertain significance (Jan 12, 2018)
6-79485772-A-C		Leber congenital amaurosis 5	Uncertain significance (Jan 13, 2018)
6-79485800-T-G		Leber congenital amaurosis 5	Uncertain significance (Jan 12, 2018)
6-79485813-A-C		Leber congenital amaurosis 5	Uncertain significance (Jan 12, 2018)
6-79485867-C-A		Leber congenital amaurosis 5	Uncertain significance (Jan 13, 2018)
6-79485887-TCAA-T			Benign (Nov 01, 2022)
6-79485891-C-T		Leber congenital amaurosis 5	Uncertain significance (Jan 13, 2018)
6-79485901-A-G		Leber congenital amaurosis 5	Uncertain significance (Jan 13, 2018)
6-79485960-T-G		Leber congenital amaurosis 5	Uncertain significance (Jan 12, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
LCA5	protein_coding	protein_coding	ENST00000392959	7	52468

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000406	1.00	125676	1	59	125736	0.000239

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.621	370	338	1.10	0.0000175	4592
Missense in Polyphen		77	84.09	0.91569		1207
Synonymous	-1.14	143	127	1.13	0.00000656	1285
Loss of Function	3.09	13	31.8	0.408	0.00000198	406

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000145	0.000145
Ashkenazi Jewish	0.00228	0.00218
East Asian	0.000326	0.000326
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000150	0.000149
Middle Eastern	0.000326	0.000326
South Asian	0.000166	0.000163
Other	0.000655	0.000652

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Might be involved in minus end-directed microtubule transport.
• Disease: DISEASE: Leber congenital amaurosis 5 (LCA5) [MIM:604537]: A severe dystrophy of the retina, typically becoming evident in the first years of life. Visual function is usually poor and often accompanied by nystagmus, sluggish or near-absent pupillary responses, photophobia, high hyperopia and keratoconus. {ECO:0000269|PubMed:17546029, ECO:0000269|PubMed:18000884, ECO:0000269|PubMed:18334959}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.111

Intolerance Scores

• loftool: 0.730
• rvis_EVS: -0.13
• rvis_percentile_EVS: 44.03

Haploinsufficiency Scores

• pHI: 0.167
• hipred: N
• hipred_score: 0.233
• ghis: 0.502

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.109

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Lca5
• Phenotype: pigmentation phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); vision/eye phenotype

Gene ontology

• Biological process: intraciliary transport
• Cellular component: microtubule organizing center;cilium;axoneme
• Molecular function: protein binding;protein-containing complex binding