NOVA2
Chr 19ADNOVA alternative splicing regulator 2
Also known as: ANOVA, NEDASB, NOVA-2, NOVA3
The NOVA2 protein regulates alternative splicing in neurons by binding to specific pre-mRNA sequences to control exon inclusion or exclusion, playing essential roles in cortical development, neural network wiring, and synapse formation. Mutations cause neurodevelopmental disorder with or without autistic features and/or structural brain abnormalities, inherited in an autosomal dominant pattern. This gene is highly intolerant to loss-of-function variants (pLI = 0.98), reflecting its critical role in neurodevelopment.
Primary Disease Associations & Inheritance
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Highly missense-constrained (top ~0.1%)
The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
132 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 10 | 0 | 7 | 0 | 17 |
Likely Pathogenic | 3 | 0 | 3 | 0 | 6 |
VUS | 3 | 55 | 15 | 1 | 74 |
Likely Benign | 0 | 2 | 3 | 19 | 24 |
Benign | 0 | 0 | 1 | 2 | 3 |
Conflicting | — | 3 | |||
| Total | 16 | 57 | 29 | 22 | 127 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
NOVA2 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools