BBS2

Bardet-Biedl syndrome 2, the group of BBSome

Basic information

Region (hg38): 16:56465639-56582667

Previous symbols: [ "BBS" ]

Links

ENSG00000125124 ∙ NCBI:583 ∙ OMIM:606151 ∙ HGNC:967 ∙ Uniprot:Q9BXC9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Bardet-Biedl syndrome 2 (Definitive), mode of inheritance: AR
• Bardet-Biedl syndrome 2 (Definitive), mode of inheritance: AR
• Bardet-Biedl syndrome 2 (Strong), mode of inheritance: AR
• Bardet-Biedl syndrome 2 (Definitive), mode of inheritance: AR
• retinitis pigmentosa (Supportive), mode of inheritance: AD
• Bardet-Biedl syndrome (Supportive), mode of inheritance: AR
• retinitis pigmentosa 74 (Definitive), mode of inheritance: AR
• Bardet-Biedl syndrome 2 (Strong), mode of inheritance: AR
• retinitis pigmentosa 74 (Strong), mode of inheritance: AR
• ciliopathy (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Bardet-Biedl syndrome 2;	AR	Endocrine	Medical management of obesity with melanocortin-4 receptor (MC4R) agonist (setmelanotide) may be beneficial	Cardiovascular; Craniofacial; Gastrointestinal; Genitourinary; Endocrine; Musculoskeletal; Neurologic; Ophthalmologic; Renal	8298649; 11285252; 11567139; 16823392; 16582908; 20120035; 20301537; 20618352; 22410627; 25541840; 36356613
Variants may modify the severity of BBS and related disorders due to variants in other BBS-associated genes

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the BBS2 gene.

• Bardet-Biedl syndrome (775 variants)
• Bardet-Biedl syndrome 2 (276 variants)
• not provided (81 variants)
• Bardet-Biedl syndrome 2;Retinitis pigmentosa 74 (68 variants)
• Inborn genetic diseases (47 variants)
• Retinitis pigmentosa 74;Bardet-Biedl syndrome 2 (33 variants)
• BBS2-related condition (28 variants)
• not specified (28 variants)
• Retinitis pigmentosa 74 (21 variants)
• Retinitis pigmentosa (10 variants)
• Retinal dystrophy (10 variants)
• Bardet-Biedl syndrome 1 (7 variants)
• Bardet-biedl syndrome 2/6, digenic (3 variants)
• Bardet-biedl syndrome 1/2, digenic (2 variants)
• See cases (1 variants)
• Autosomal recessive retinitis pigmentosa (1 variants)
• Bardet-biedl syndrome 2/4, digenic (1 variants)
• BBS2-Related Disorders (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the BBS2 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	229	1	232
missense	3	7	247	5	3	265
nonsense	11	33	1			45
start loss						0
frameshift	31	51	1			83
inframe indel		1	4			5
splice donor/acceptor (+/-2bp)	9	39	1			49
splice region		1	18	48		67
non coding			43	92	29	164
Total	54	131	299	326	33

Highest pathogenic variant AF is 0.0000986

Variants in BBS2

This is a list of pathogenic ClinVar variants found in the BBS2 region.

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

Position	Type	Phenotype	Significance	ClinVar
16-56466188-G-A		not specified	Uncertain significance (Jul 13, 2022)
16-56466191-G-T		not specified	Uncertain significance (Nov 08, 2022)
16-56466918-C-T		not specified	Uncertain significance (Jul 09, 2021)
16-56466941-G-A		not specified	Uncertain significance (Nov 17, 2023)
16-56466945-T-C		not specified	Uncertain significance (Aug 02, 2023)
16-56467210-G-A		not specified	Uncertain significance (Oct 30, 2023)
16-56467267-C-A		not specified	Uncertain significance (Aug 02, 2023)
16-56467270-C-T		not specified	Uncertain significance (Jul 05, 2023)
16-56467279-C-T		not specified	Uncertain significance (Dec 07, 2021)
16-56467962-C-A		not specified	Uncertain significance (Dec 19, 2022)
16-56467972-A-G		not specified	Uncertain significance (Oct 06, 2021)
16-56470030-G-A		not specified	Uncertain significance (Dec 27, 2023)
16-56470056-G-C		not specified	Uncertain significance (Mar 01, 2023)
16-56470618-C-T		not specified	Uncertain significance (Mar 29, 2023)
16-56470787-G-C		not specified	Uncertain significance (Jan 23, 2024)
16-56475542-A-T		not specified	Uncertain significance (Sep 27, 2021)
16-56475571-TTTC-T		Bardet-Biedl syndrome 2;Retinitis pigmentosa 74	Uncertain significance (Mar 29, 2022)
16-56476086-T-C		not specified	Uncertain significance (Jan 09, 2024)
16-56476123-T-C		not specified	Uncertain significance (Dec 15, 2022)
16-56476132-G-A		not specified	Uncertain significance (Oct 14, 2021)
16-56476159-C-G		not specified	Uncertain significance (Aug 02, 2021)
16-56476160-A-C			Benign (Jan 01, 2024)
16-56476185-T-G		not specified	Uncertain significance (Apr 07, 2022)
16-56484445-T-C		Bardet-Biedl syndrome 2	Benign (Jan 13, 2018)
16-56484670-G-A		Bardet-Biedl syndrome 2	Uncertain significance (Jan 12, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
BBS2	protein_coding	protein_coding	ENST00000245157	17	53448

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.03e-17	0.123	125556	0	192	125748	0.000764

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.870	351	400	0.878	0.0000226	4752
Missense in Polyphen		125	148.28	0.843		1781
Synonymous	0.243	143	147	0.975	0.00000775	1426
Loss of Function	1.22	31	39.3	0.790	0.00000262	410

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000387	0.000387
Ashkenazi Jewish	0.0000993	0.0000992
East Asian	0.00223	0.00223
Finnish	0.000878	0.000878
European (Non-Finnish)	0.000907	0.000906
Middle Eastern	0.00223	0.00223
South Asian	0.000425	0.000425
Other	0.000816	0.000815

dbNSFP

Source: dbNSFP

• Function: FUNCTION: The BBSome complex is thought to function as a coat complex required for sorting of specific membrane proteins to the primary cilia. The BBSome complex is required for ciliogenesis but is dispensable for centriolar satellite function. This ciliogenic function is mediated in part by the Rab8 GDP/GTP exchange factor, which localizes to the basal body and contacts the BBSome. Rab8(GTP) enters the primary cilium and promotes extension of the ciliary membrane. Firstly the BBSome associates with the ciliary membrane and binds to RAB3IP/Rabin8, the guanosyl exchange factor (GEF) for Rab8 and then the Rab8-GTP localizes to the cilium and promotes docking and fusion of carrier vesicles to the base of the ciliary membrane. The BBSome complex, together with the LTZL1, controls SMO ciliary trafficking and contributes to the sonic hedgehog (SHH) pathway regulation. Required for proper BBSome complex assembly and its ciliary localization. {ECO:0000269|PubMed:17574030, ECO:0000269|PubMed:22072986}.
• Disease: DISEASE: Retinitis pigmentosa 74 (RP74) [MIM:616562]: A retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well. {ECO:0000269|PubMed:25541840}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: BBSome-mediated cargo-targeting to cilium;Cargo trafficking to the periciliary membrane;Cilium Assembly;Organelle biogenesis and maintenance (Consensus)

Recessive Scores

• pRec: 0.0955

Intolerance Scores

• loftool: 0.233
• rvis_EVS: -0.84
• rvis_percentile_EVS: 11.36

Haploinsufficiency Scores

• pHI: 0.180
• hipred: N
• hipred_score: 0.372
• ghis: 0.575

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.805

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Bbs2
• Phenotype: adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); endocrine/exocrine gland phenotype; taste/olfaction phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; cellular phenotype; homeostasis/metabolism phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); liver/biliary system phenotype; normal phenotype; reproductive system phenotype; vision/eye 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); digestive/alimentary phenotype; renal/urinary system phenotype

Zebrafish Information Network

• Gene name: bbs2
• Affected structure: pronephric proximal convoluted tubule
• Phenotype tag: abnormal
• Phenotype quality: morphology

Gene ontology

• Biological process: sperm axoneme assembly;visual perception;protein localization;negative regulation of gene expression;artery smooth muscle contraction;striatum development;hippocampus development;cerebral cortex development;adult behavior;melanosome transport;protein localization to organelle;negative regulation of appetite by leptin-mediated signaling pathway;negative regulation of multicellular organism growth;positive regulation of multicellular organism growth;vasodilation;Golgi to plasma membrane protein transport;fat cell differentiation;photoreceptor cell maintenance;brain morphogenesis;cartilage development;cilium assembly;regulation of cilium beat frequency involved in ciliary motility;non-motile cilium assembly
• Cellular component: cytosol;microvillus;membrane;motile cilium;stereocilium;BBSome;ciliary basal body;ciliary membrane
• Molecular function: RNA polymerase II repressing transcription factor binding;protein binding