GeneBe

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

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Spinal muscular atrophy, lower extremity-predominant, 2A, childhood onset, autosomal dominant; Spinal muscular atrophy, lower extremity-predominant, 2B, prenatal onset, autosomal dominantADGeneralGenetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testingCraniofacial; Musculoskeletal; Neurologic23664116; 23664119; 23664120; 27751653; 28635954; 30054298

ClinVar

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

  • Autosomal_dominant_childhood-onset_proximal_spinal_muscular_atrophy_with_contractures (759 variants)
  • Inborn_genetic_diseases (192 variants)
  • not_provided (153 variants)
  • not_specified (48 variants)
  • BICD2-related_disorder (35 variants)
  • Spinal_muscular_atrophy,_lower_extremity-predominant,_2b,_prenatal_onset,_autosomal_dominant (15 variants)
  • Neuronopathy,_distal_hereditary_motor,_autosomal_dominant (5 variants)
  • Spastic_paraplegia (3 variants)
  • Charcot-Marie-Tooth_disease (2 variants)
  • Hereditary_spastic_paraplegia (2 variants)
  • Hereditary_spastic_paraplegia_3A (2 variants)
  • Autosomal_dominant_hereditary_axonal_motor_and_sensory_neuropathy (1 variants)
  • EEG_abnormality (1 variants)
  • Distal_myopathy (1 variants)
  • Autosomal_dominant_childhood-onset_proximal_spinal_muscular_atrophy_without_contractures (1 variants)
  • Autism_spectrum_disorder (1 variants)
  • Spinal_muscular_atrophy_with_lower_extremity_predominance (1 variants)
  • Recurrent_metabolic_encephalomyopathic_crises-rhabdomyolysis-cardiac_arrhythmia-intellectual_disability_syndrome (1 variants)
  • Amyotrophic_lateral_sclerosis (1 variants)
  • Decreased_fetal_movement (1 variants)
  • Feeding_difficulties (1 variants)
  • Muscular_atrophy (1 variants)
  • Tapered_finger (1 variants)
  • Seizure (1 variants)
  • Open_mouth (1 variants)
  • Arthrogryposis_multiplex_congenita (1 variants)
  • Muscle_weakness (1 variants)
  • Spinal_muscular_atrophy,_lower_extremity-predominant,_2,_AD (1 variants)
  • BICD2-related_Autosomal_recessive_Cohen_Like_syndrome (1 variants)
  • Spinal_muscular_atrophy (1 variants)
  • Neuronopathy,_distal_hereditary_motor,_type_5B (1 variants)
  • Cerebral_cortical_atrophy (1 variants)
  • Recurrent_fractures (1 variants)
  • Absent_speech (1 variants)
  • Pelvic_girdle_muscle_weakness (1 variants)
  • Downturned_corners_of_mouth (1 variants)
  • Macrocephaly (1 variants)
  • Myopathy (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. These statistics are base on transcript: NM_001003800.2. Only rare variants are included in the table.

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.

EffectPLPVUSLBBSum
synonymous
2
clinvar
243
clinvar
10
clinvar
 255
missense
11
clinvar
28
clinvar
342
clinvar
125
clinvar
9
clinvar
 515
nonsense
1
clinvar
1
clinvar
7
clinvar
 9
start loss
1
 1
frameshift
5
clinvar
 5
splice donor/acceptor (+/-2bp)
1
clinvar
 1
Total 12 29 358 368 19

Highest pathogenic variant AF is 0.0000013693096

Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
BICD2protein_codingprotein_codingENST00000356884 753450
pLI Probability
LOF Intolerant 		pRec Probability
LOF Recessive 		Individuals with
no LOFs 		Individuals with
Homozygous LOFs 		Individuals with
Heterozygous LOFs 		Defined p
0.9830.01731257320141257460.0000557
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense2.214145610.7380.00003995544
Missense in Polyphen120230.690.520182319
Synonymous-0.4462602511.040.00001801745
Loss of Function4.40430.00.1330.00000137370

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.0002140.000151
Ashkenazi Jewish0.000.00
East Asian0.0001090.000109
Finnish0.000.00
European (Non-Finnish)0.00004640.0000439
Middle Eastern0.0001090.000109
South Asian0.0001650.0000980
Other0.000.00

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

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

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