B9D2

B9 domain containing 2, the group of MKS complex|B9 domain containing

Basic information

Region (hg38): 19:41354417-41364165

Links

ENSG00000123810 ∙ NCBI:80776 ∙ OMIM:611951 ∙ HGNC:28636 ∙ Uniprot:Q9BPU9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Meckel syndrome, type 10 (Strong), mode of inheritance: AR
• Meckel syndrome (Supportive), mode of inheritance: AR
• ciliopathy (Moderate), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Meckel syndrome 10	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	Gastrointestinal; Musculoskeletal; Neurologic; Renal	21763481

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the B9D2 gene.

• Joubert syndrome and related disorders (1 variants)
• Familial aplasia of the vermis (1 variants)
• Joubert syndrome 34 (1 variants)
• Meckel syndrome, type 10 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the B9D2 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				17		17
missense	2	3	25	2	1	33
nonsense		1				1
start loss						0
frameshift		3				3
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			1	1		2
non coding				5	8	13
Total	2	7	25	24	9

Variants in B9D2

This is a list of pathogenic ClinVar variants found in the B9D2 region.

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

Position	Type	Phenotype	Significance	ClinVar
19-41354682-C-T		not specified • Meckel-Gruber syndrome;Familial aplasia of the vermis • Meckel syndrome, type 10	Benign (Sep 11, 2023)
19-41354712-G-A		Meckel-Gruber syndrome;Familial aplasia of the vermis	Likely benign (Jan 15, 2024)
19-41354712-G-T		B9D2-related disorder	Likely benign (Feb 21, 2019)
19-41354714-C-T		not specified	Uncertain significance (Apr 12, 2024)
19-41354715-G-A		not specified • Meckel-Gruber syndrome;Familial aplasia of the vermis	Benign/Likely benign (Jul 20, 2023)
19-41354719-C-T		Familial aplasia of the vermis;Meckel-Gruber syndrome	Uncertain significance (Jun 01, 2022)
19-41354720-G-A		Meckel-Gruber syndrome;Familial aplasia of the vermis	Uncertain significance (May 19, 2022)
19-41354720-G-C		Meckel-Gruber syndrome;Familial aplasia of the vermis	Uncertain significance (Sep 01, 2021)
19-41354722-T-TCGAAGTTG		not specified	Uncertain significance (Oct 15, 2024)
19-41354732-G-A		Meckel syndrome, type 10 • not specified	Uncertain significance (Apr 04, 2024)
19-41354733-G-A		Meckel-Gruber syndrome;Familial aplasia of the vermis	Likely benign (Dec 31, 2019)
19-41354738-G-A			Likely benign (Oct 01, 2024)
19-41354744-C-A		Meckel syndrome, type 10 • not specified • Familial aplasia of the vermis;Meckel-Gruber syndrome	Uncertain significance (Aug 25, 2024)
19-41354744-C-T		Meckel-Gruber syndrome;Familial aplasia of the vermis	Uncertain significance (May 03, 2022)
19-41354745-G-A			Likely benign (Apr 10, 2018)
19-41354765-C-T		Familial aplasia of the vermis • Joubert syndrome and related disorders • Joubert syndrome 34	Pathogenic/Likely pathogenic (Feb 18, 2022)
19-41354767-C-A		not specified	Uncertain significance (Jul 25, 2023)
19-41354785-C-T		not specified	Uncertain significance (Dec 13, 2023)
19-41354796-G-A		Meckel-Gruber syndrome;Familial aplasia of the vermis	Likely benign (Jun 06, 2023)
19-41354800-C-G		not specified	Uncertain significance (May 27, 2022)
19-41354847-G-A			Likely benign (Jul 18, 2018)
19-41354854-C-T		Familial aplasia of the vermis;Meckel-Gruber syndrome	Uncertain significance (Oct 13, 2023)
19-41354869-C-T		not specified	Uncertain significance (Dec 09, 2023)
19-41354882-G-A		Meckel-Gruber syndrome;Familial aplasia of the vermis	Likely benign (Mar 01, 2017)
19-41354892-C-T		Meckel-Gruber syndrome;Familial aplasia of the vermis • B9D2-related disorder	Likely benign (Aug 09, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
B9D2	protein_coding	protein_coding	ENST00000243578	3	9753

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000526	0.456	125708	0	23	125731	0.0000915

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.130	124	120	1.03	0.00000853	1123
Missense in Polyphen		35	39.925	0.87663		344
Synonymous	0.170	50	51.6	0.970	0.00000384	363
Loss of Function	0.380	7	8.17	0.857	4.37e-7	69

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000213	0.000213
Ashkenazi Jewish	0.000426	0.000397
East Asian	0.00	0.00
Finnish	0.0000988	0.0000924
European (Non-Finnish)	0.0000805	0.0000791
Middle Eastern	0.00	0.00
South Asian	0.0000980	0.0000980
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Component of the tectonic-like complex, a complex localized at the transition zone of primary cilia and acting as a barrier that prevents diffusion of transmembrane proteins between the cilia and plasma membranes. {ECO:0000269|PubMed:21763481}.
• Disease: DISEASE: Meckel syndrome 10 (MKS10) [MIM:614175]: A disorder characterized by a combination of renal cysts and variably associated features including developmental anomalies of the central nervous system (typically encephalocele), hepatic ductal dysplasia and cysts, and polydactyly. {ECO:0000269|PubMed:21763481}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Joubert syndrome 34 (JBTS34) [MIM:614175]: A form of Joubert syndrome, a disorder presenting with cerebellar ataxia, oculomotor apraxia, hypotonia, neonatal breathing abnormalities and psychomotor delay. Neuroradiologically, it is characterized by cerebellar vermian hypoplasia/aplasia, thickened and reoriented superior cerebellar peduncles, and an abnormally large interpeduncular fossa, giving the appearance of a molar tooth on transaxial slices (molar tooth sign). Additional variable features include retinal dystrophy, renal disease, liver fibrosis, and polydactyly. JBTS34 inheritance is autosomal recessive. {ECO:0000269|PubMed:26092869}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Signal Transduction;Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal;Amplification of signal from the kinetochores;Mitotic Spindle Checkpoint;Cell Cycle Checkpoints;RHO GTPases Activate Formins;RHO GTPase Effectors;Signaling by Rho GTPases;Mitotic Prometaphase;Separation of Sister Chromatids;Mitotic Anaphase;Mitotic Metaphase and Anaphase;M Phase;Cell Cycle;Resolution of Sister Chromatid Cohesion;Cell Cycle, Mitotic;Anchoring of the basal body to the plasma membrane;Cilium Assembly;Organelle biogenesis and maintenance (Consensus)

Recessive Scores

• pRec: 0.133

Intolerance Scores

• loftool: 0.574
• rvis_EVS: -0.12
• rvis_percentile_EVS: 44.89

Haploinsufficiency Scores

• pHI: 0.142
• hipred: N
• hipred_score: 0.344
• ghis: 0.566

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.481

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: B9d2
• Phenotype: growth/size/body region phenotype; endocrine/exocrine gland phenotype; homeostasis/metabolism phenotype; cellular phenotype; muscle phenotype; craniofacial phenotype; vision/eye 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); hematopoietic 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); reproductive system phenotype; neoplasm; embryo phenotype; respiratory system phenotype; liver/biliary system phenotype; immune system phenotype; skeleton phenotype; renal/urinary system phenotype; digestive/alimentary 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); limbs/digits/tail phenotype

Zebrafish Information Network

• Gene name: b9d2
• Affected structure: photoreceptor cell
• Phenotype tag: abnormal
• Phenotype quality: morphology

Gene ontology

• Biological process: cilium assembly;ciliary basal body-plasma membrane docking
• Cellular component: nucleus;centrosome;cytosol;membrane;MKS complex;ciliary basal body
• Molecular function: protein binding;gamma-tubulin binding