VWA3B

protein-coding

von Willebrand factor A domain containing 3B

Gene summary

This gene encodes an intracellular protein that contains a von Willebrand factor type A domain. Intracellular proteins with VWA domains are thought to function in transcription, DNA repair, ribosomal and membrane transport and the proteasome. Mutations in this gene are associated with Spinocerebellar ataxia, autosomal recessive 22. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, May 2017]

MANE transcript

NM_144992.5

Inheritance

ClinVar variants

P:12U:198B:58

Top phenotype

Spinocerebellar ataxia, autosomal recessive 22

gnomAD constraint

pLI —, LoF o/e 0.75

Max pathogenic AF

—

Genomic locus

chr2:98,087,116-98,313,299

External References & Databases

Ensembl (ENSG00000168658)

Transcript & Mutation Effects

hg38 • Region Span ~226.2 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

spinocerebellar ataxia, autosomal recessive 22LIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0014845

Submitter: PMGRC

spinocerebellar ataxia, autosomal recessive 22LIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0014845

Submitter: PanelApp Australia

spinocerebellar ataxia, autosomal recessive 22LIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0014845

Submitter: Labcorp Genetics (formerly Invitae)

spinocerebellar ataxia, autosomal recessive 22LIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0014845

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Spinocerebellar ataxia, autosomal recessive 22AR

Manifestation: Neurologic

Intervention: General

Rationale: 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

Refs: 26157035

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to VWA3B variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 209

not providedTotal: 41

Spinocerebellar ataxia, autosomal recessive 22Total: 17

VWA3B-related disorderTotal: 15

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_144992.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar	21 clinvar	5 clinvar	28
missense	1 clinvar	1 clinvar	183 clinvar	27 clinvar	3 clinvar	215
nonsense		2 clinvar	3 clinvar	1 clinvar	1 clinvar	7
start loss						0
frameshift		6 clinvar	7 clinvar			13
splice donor/acceptor (+/-2bp)		2 clinvar	3 clinvar			5
Total	1	11	198	49	9	268

Highest pathogenic variant AF is 0.000061339204

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 31 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_144992.5	RefSeq	NP_659429.4	27	MANE Select
ENST00000477737.6	Ensembl	ENSP00000417955.1	27	MANE Select
NM_001345864.2	RefSeq	NP_001332793.1	21	Standard
ENST00000416277.5	Ensembl	ENSP00000411168.1	9	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Cellular Component

cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000477737
Coding exons: 27
Length: 226184
Individuals with no LoFs: 116831
Homozygous LoFs: 182
Heterozygous LoFs: 7810
Defined: 124823
p: 0.0325

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.259	678	697	0.972	0.0000374	8465
Missense (PolyPhen)		183	182.47	1.0029		2292
Synonymous	0.341	270	277	0.974	0.0000164	2445
Loss of Function	1.97	52	69.7	0.746	0.00000357	832

Population LoF Frequency

Population	CAF	p-value	Status
African	0.033	0.033	notable
Latino/Admixed American	0.014	0.014	notable
Ashkenazi Jewish	0.019	0.019	notable
East Asian	0.0092	0.0091	notable
Finnish	0.029	0.029	notable
European (Non-Finnish)	0.048	0.048	notable
South Asian	0.019	0.019	notable
Other	0.033	0.032	notable

dbNSFP Gene Annotations

Source: dbNSFP

Disease: DISEASE: Spinocerebellar ataxia, autosomal recessive, 22 (SCAR22) [MIM:616948]: A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCAR22 patients manifest variable severity of intellectual disability associated with adult-onset cerebellar ataxia. {ECO:0000269|PubMed:26157035}. Note=The disease may be caused by mutations affecting the gene represented in this entry.;

Intolerance Scores

LoFtool: 0.959
RVIS EVS: 1.32
RVIS percentile EVS: 94.08

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.195

Gene Damage Prediction

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