BICD2

BICD cargo adaptor 2

Basic information

Region (hg38): 9:92711363-92764833

Links

ENSG00000185963 ∙ NCBI:23299 ∙ OMIM:609797 ∙ HGNC:17208 ∙ Uniprot:Q8TD16 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal dominant childhood-onset proximal spinal muscular atrophy with contractures (Strong), mode of inheritance: AD
• autosomal dominant childhood-onset proximal spinal muscular atrophy with contractures (Strong), mode of inheritance: AD
• autosomal dominant childhood-onset proximal spinal muscular atrophy with contractures (Supportive), mode of inheritance: AD
• autosomal dominant childhood-onset proximal spinal muscular atrophy with contractures (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Spinal muscular atrophy, lower extremity-predominant, 2A, childhood onset, autosomal dominant; Spinal muscular atrophy, lower extremity-predominant, 2B, prenatal onset, autosomal dominant	AD	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	Craniofacial; Musculoskeletal; Neurologic	23664116; 23664119; 23664120; 27751653; 28635954; 30054298

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the BICD2 gene.

• not provided (4 variants)
• Autosomal dominant childhood-onset proximal spinal muscular atrophy with contractures (3 variants)
• Neuronopathy, distal hereditary motor, autosomal dominant (1 variants)
• Spinal muscular atrophy with lower extremity predominance (1 variants)
• Spastic paraplegia (1 variants)
• Spinal muscular atrophy (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the BICD2 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			5	219	8	232
missense	6	20	287	79	8	400
nonsense		1	4			5
start loss			1			1
frameshift			4			4
inframe indel	1	2	18			21
splice donor/acceptor (+/-2bp)			1			1
splice region			8	13		21
non coding			1	49	17	67
Total	7	23	321	347	33

Variants in BICD2

This is a list of pathogenic ClinVar variants found in the BICD2 region.

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

Position	Type	Phenotype	Significance	ClinVar
9-92713365-G-T			Benign (Jun 28, 2018)
9-92713655-G-A			Benign (Jun 26, 2018)
9-92715018-C-T			Likely benign (Oct 24, 2018)
9-92715134-C-T		not specified	Likely benign (Jul 21, 2016)
9-92715159-C-T		Autosomal dominant childhood-onset proximal spinal muscular atrophy with contractures	Uncertain significance (Sep 20, 2022)
9-92715163-G-A		Autosomal dominant childhood-onset proximal spinal muscular atrophy with contractures	Likely benign (Apr 05, 2023)
9-92715175-C-A		Autosomal dominant childhood-onset proximal spinal muscular atrophy with contractures	Uncertain significance (Aug 04, 2023)
9-92715177-T-G		Autosomal dominant childhood-onset proximal spinal muscular atrophy with contractures • Inborn genetic diseases	Uncertain significance (Nov 20, 2023)
9-92715178-C-T		Autosomal dominant childhood-onset proximal spinal muscular atrophy with contractures • BICD2-related disorder	Benign (Aug 25, 2023)
9-92715180-C-T		Autosomal dominant childhood-onset proximal spinal muscular atrophy with contractures	Uncertain significance (Jul 26, 2021)
9-92715181-G-A		Autosomal dominant childhood-onset proximal spinal muscular atrophy with contractures • BICD2-related disorder	Benign (Aug 27, 2023)
9-92715186-A-G		Autosomal dominant childhood-onset proximal spinal muscular atrophy with contractures	Likely benign (Nov 21, 2023)
9-92715195-G-A		Autosomal dominant childhood-onset proximal spinal muscular atrophy with contractures	Uncertain significance (Nov 15, 2022)
9-92715195-G-C		Autosomal dominant childhood-onset proximal spinal muscular atrophy with contractures	Likely benign (Sep 03, 2023)
9-92715207-C-T		Autosomal dominant childhood-onset proximal spinal muscular atrophy with contractures • Spastic paraplegia • Inborn genetic diseases	Conflicting classifications of pathogenicity (Dec 15, 2023)
9-92715208-G-A		Autosomal dominant childhood-onset proximal spinal muscular atrophy with contractures	Likely benign (Aug 07, 2023)
9-92715212-C-A		Autosomal dominant childhood-onset proximal spinal muscular atrophy with contractures	Uncertain significance (Feb 06, 2023)
9-92715216-C-T		Autosomal dominant childhood-onset proximal spinal muscular atrophy with contractures	Likely benign (Oct 10, 2023)
9-92715217-G-A		BICD2-related disorder	Likely benign (Dec 07, 2017)
9-92715222-T-C		Autosomal dominant childhood-onset proximal spinal muscular atrophy with contractures	Likely benign (Aug 23, 2022)
9-92715225-C-T		Inborn genetic diseases • Autosomal dominant childhood-onset proximal spinal muscular atrophy with contractures	Benign/Likely benign (Aug 10, 2023)
9-92715226-G-A		Autosomal dominant childhood-onset proximal spinal muscular atrophy with contractures	Likely benign (Mar 18, 2022)
9-92715229-G-A		Autosomal dominant childhood-onset proximal spinal muscular atrophy with contractures	Likely benign (Sep 23, 2023)
9-92715237-C-T		Autosomal dominant childhood-onset proximal spinal muscular atrophy with contractures	Uncertain significance (Apr 26, 2022)
9-92715241-G-C		Autosomal dominant childhood-onset proximal spinal muscular atrophy with contractures	Likely benign (May 10, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
BICD2	protein_coding	protein_coding	ENST00000356884	7	53450

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.983	0.0173	125732	0	14	125746	0.0000557

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.21	414	561	0.738	0.0000399	5544
Missense in Polyphen		120	230.69	0.52018		2319
Synonymous	-0.446	260	251	1.04	0.0000180	1745
Loss of Function	4.40	4	30.0	0.133	0.00000137	370

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000214	0.000151
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.0000464	0.0000439
Middle Eastern	0.000109	0.000109
South Asian	0.000165	0.0000980
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Acts as an adapter protein linking the dynein motor complex to various cargos and converts dynein from a non- processive to a highly processive motor in the presence of dynactin. Facilitates and stabilizes the interaction between dynein and dynactin and activates dynein processivity (the ability to move along a microtubule for a long distance without falling off the track) (By similarity). Facilitates the binding of RAB6A to the Golgi by stabilizing its GTP-bound form. Regulates coat complex coatomer protein I (COPI)-independent Golgi-endoplasmic reticulum transport via its interaction with RAB6A and recruitment of the dynein-dynactin motor complex (PubMed:25962623). Contributes to nuclear and centrosomal positioning prior to mitotic entry through regulation of both dynein and kinesin-1. During G2 phase of the cell cycle, associates with RANBP2 at the nuclear pores and recruits dynein and dynactin to the nuclear envelope to ensure proper positioning of the nucleus relative to centrosomes prior to the onset of mitosis (By similarity). {ECO:0000250|UniProtKB:Q921C5, ECO:0000269|PubMed:25962623}.
• Disease: DISEASE: Spinal muscular atrophy, lower extremity-predominant 2, autosomal dominant (SMALED2) [MIM:615290]: An autosomal dominant form of spinal muscular atrophy characterized by early-childhood onset of muscle weakness and atrophy predominantly affecting the proximal and distal muscles of the lower extremity, although some patients may show upper extremity involvement. The disorder results in delayed walking, waddling gait, difficulty walking, and loss of distal reflexes. Some patients may have foot deformities or hyperlordosis, and some show mild upper motor signs, such as spasticity. Sensation, bulbar function, and cognitive function are preserved. The disorder shows very slow progression throughout life. {ECO:0000269|PubMed:23664116, ECO:0000269|PubMed:23664119, ECO:0000269|PubMed:23664120}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Vesicle-mediated transport;Membrane Trafficking;COPI-independent Golgi-to-ER retrograde traffic;Golgi-to-ER retrograde transport;Intra-Golgi and retrograde Golgi-to-ER traffic (Consensus)

Recessive Scores

• pRec: 0.110

Intolerance Scores

• loftool: 0.468
• rvis_EVS: -1.39
• rvis_percentile_EVS: 4.25

Haploinsufficiency Scores

• pHI: 0.218
• hipred: Y
• hipred_score: 0.707
• ghis: 0.606

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.918

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Bicd2
• 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); skeleton 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); growth/size/body region phenotype; cellular phenotype; craniofacial phenotype

Gene ontology

• Biological process: retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum;protein transport;protein localization to Golgi apparatus;mRNA transport;centrosome localization;regulation of microtubule cytoskeleton organization;minus-end-directed organelle transport along microtubule;microtubule anchoring at microtubule organizing center
• Cellular component: nuclear envelope;annulate lamellae;nuclear pore;cytoplasm;Golgi apparatus;centrosome;cytosol;plasma membrane;cytoplasmic vesicle
• Molecular function: protein binding;cytoskeletal adaptor activity;Rab GTPase binding;dynactin binding;dynein light intermediate chain binding;dynein complex binding