VWA2

protein-coding

von Willebrand factor A domain containing 2

Gene summary

This gene encodes a member of the von Willebrand factor A-like domain protein superfamily. The encoded protein is localized to the extracellular matrix and may serve as a structural component in basement membranes or in anchoring structures on scaffolds of collagen VII or fibrillin. This gene has been linked to type 1A diabetes and is a candidate serological marker for colon cancer. [provided by RefSeq, Jan 2013]

MANE transcript

NM_001272046.2

Inheritance

ClinVar variants

P:1U:15B:44

Top phenotype

VWA2-related disorder

gnomAD constraint

pLI —, LoF o/e 1

Max pathogenic AF

—

Genomic locus

chr10:114,239,254-114,294,489

External References & Databases

Ensembl (ENSG00000165816)

Transcript & Mutation Effects

hg38 • Region Span ~55.2 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

congenital anomaly of kidney and urinary tractLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0019719

Submitter: Ambry Genetics

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to VWA2 variants in ClinVar

3 Conditions Cataloged

VWA2-related disorderTotal: 42

not providedTotal: 26

Vesicoureteral refluxTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001272046.2. 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			3 clinvar	15 clinvar	10 clinvar	28
missense		1 clinvar	12 clinvar	9 clinvar	9 clinvar	31
nonsense						0
start loss						0
frameshift				1 clinvar		1
splice donor/acceptor (+/-2bp)						0
Total	0	1	15	25	19	60

Highest pathogenic variant AF is 0.00038003596

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 16 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001272046.2	RefSeq	NP_001258975.1	13	MANE Select
ENST00000392982.8	Ensembl	ENSP00000376708.3	13	MANE Select
NM_001320804.1	RefSeq	NP_001307733.1	13	Standard
ENST00000603594.2	Ensembl	ENSP00000473752.2	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

growth plate cartilage chondrocyte morphogenesis
calcium-independent cell-matrix adhesion
regulation of insulin receptor signaling pathway
protein homooligomerization

Molecular Function

calcium ion binding
protein binding
identical protein binding

Cellular Component

basement membrane
extracellular space
extracellular matrix
extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000603594
Coding exons: 11
Length: 52255
Individuals with no LoFs: 125403
Homozygous LoFs: 2
Heterozygous LoFs: 343
Defined: 125748
p: 0.00137

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.0123	457	456	1.00	0.0000288	4642
Missense (PolyPhen)		131	127.95	1.0238		1568
Synonymous	-0.0506	201	200	1.00	0.0000132	1580
Loss of Function	0.00627	26	26.0	0.999	0.00000127	304

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00031	0.00031	rare
Latino/Admixed American	0.0041	0.0041	notable
Ashkenazi Jewish	0	0.0	absent
East Asian	0.0038	0.0036	notable
Finnish	0.00014	0.00014	rare
European (Non-Finnish)	0.00057	0.00056	rare
South Asian	0.0020	0.0019	notable
Other	0.0012	0.0011	notable

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.101

Intolerance Scores

LoFtool: 0.258
RVIS EVS: 0.12
RVIS percentile EVS: 62.24

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Indispensability pred.: N
Indispensability score: 0.150

Gene Damage Prediction

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