VWC2L

Chr 2

von Willebrand factor C domain containing 2 like

NCBI Gene: 402117 ENSG00000174453 UniProt: B2RUY7 OMIM: 619794

Predicted to be involved in negative regulation of BMP signaling pathway. Predicted to act upstream of or within positive regulation of neuron differentiation. Predicted to be located in extracellular region and synapse. Predicted to be part of AMPA glutamate receptor complex. Predicted to be active in extracellular space. [provided by Alliance of Genome Resources, Jul 2025]

OMIM Research

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 0.80

Clinical Summary— VWC2L

⚡

Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.31) despite low pLI — interpret in context.

📋

ClinVar Variants

23 VUS of 25 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.80LOEUF

pLI 0.130

Z-score 2.00

OE 0.31 (0.14–0.80)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.55Z-score

OE missense 0.61 (0.51–0.74)

78 obs / 127.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.31 (0.14–0.80)

0≤0.351.4

Missense OE?0.61 (0.51–0.74)

0≤0.61.4

Synonymous OE?0.98

0≤1.21.6

LoF obs/exp: 3 / 9.8Missense obs/exp: 78 / 127.0Syn Z: 0.09

This gene — mechanism propensity

0.6260th %ile

GOF

0.6737th %ile

LOF

0.3066th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

25 submitted variants in ClinVar

ClinVar

Classification Summary

VUS23

VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	3	20	23
Likely Benign	0	0	0
Benign	0	0	0
Total	3	20	23

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

20 pathogenic / likely-pathogenic (of 30) ClinVar copy-number / structural variants overlap VWC2L — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →