Human Gene Module / Chromosome 19 / NOVA2

NOVA2NOVA alternative splicing regulator 2

SFARI Gene Score
S
Syndromic Syndromic
Autism Reports / Total Reports
1 / 3
Rare Variants / Common Variants
16 / 0
Aliases
NOVA2, ANOVA,  NOVA3
Associated Syndromes
-
Chromosome Band
19q13.32
Associated Disorders
ASD
Relevance to Autism

Mattioli et al., 2020 reported six individuals with frameshift variants in the NOVA2 gene affected with a severe neurodevelopmental disorder characterized by intellectual disability, motor and speech delay, autistic features, hypotonia, feeding difficulties, spasticity or ataxic gait, and abnormal brain MRI. Scala et al., 2022 investigated eight individuals with seven novel pathogenic NOVA2 variants; all eight individuals presented with global developmental delay and intellectual disability, and autistic features/autism spectrum disorder was observed in six individuals.

Molecular Function

May regulate RNA splicing or metabolism in a specific subset of developing neurons

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to NOVA2 (3 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary De Novo Frameshift Variants in the Neuronal Splicing Factor NOVA2 Result in a Common C-Terminal Extension and Cause a Severe Form of Neurodevelopmental Disorder Mattioli F et al. (2020) No ASD or autistic features, stereotypy
2 Recent Recommendation - Scala M et al. (2022) No ASD or autistic features, ADHD, epilepsy/seizures
3 Support - Zhou X et al. (2022) Yes -
Rare Variants   (16)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.371C>T p.Thr124Met missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.488G>C p.Trp163Ser missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.256C>T p.Gln86Ter stop_gained De novo - Simplex 35607920 Scala M et al. (2022)
c.1050C>T p.Pro350%3D synonymous_variant De novo - - 35982159 Zhou X et al. (2022)
c.523del p.Leu175CysfsTer6 frameshift_variant De novo - - 35607920 Scala M et al. (2022)
c.755_764del p.Leu252ProfsTer141 frameshift_variant De novo - - 35607920 Scala M et al. (2022)
c.787del p.Ala263ProfsTer133 frameshift_variant De novo - Simplex 35607920 Scala M et al. (2022)
c.826del p.Leu276CysfsTer120 frameshift_variant De novo - Simplex 35607920 Scala M et al. (2022)
c.782del p.Val261GlyfsTer135 frameshift_variant De novo - Simplex 32197073 Mattioli F et al. (2020)
c.709_748del p.Val237ProfsTer146 frameshift_variant De novo - Unknown 32197073 Mattioli F et al. (2020)
c.754_756delinsTT p.Leu252PhefsTer144 frameshift_variant De novo - Simplex 35607920 Scala M et al. (2022)
c.710_711insTG p.Leu238GlyfsTer159 frameshift_variant De novo - Simplex 32197073 Mattioli F et al. (2020)
c.1329dup p.Lys444GlnfsTer82 frameshift_variant Unknown Not maternal Unknown 35607920 Scala M et al. (2022)
c.781del p.Val261TrpfsTer135 frameshift_variant Unknown Not maternal Simplex 32197073 Mattioli F et al. (2020)
c.702_703insCCCGCGGATGTGCTGCCAGC p.Ala235ProfsTer168 frameshift_variant De novo - Simplex 32197073 Mattioli F et al. (2020)
c.720_721insCCGCGGATGTGCTTCCAGCC p.Ala241ProfsTer162 frameshift_variant De novo - Simplex 32197073 Mattioli F et al. (2020)
Common Variants  

No common variants reported.

SFARI Gene score
S

Syndromic

Score Delta: Score remained at S

criteria met
See SFARI Gene'scoring criteria
S

Syndromic

See all Category S Genes

The syndromic category includes mutations that are associated with a substantial degree of increased risk and consistently linked to additional characteristics not required for an ASD diagnosis. If there is independent evidence implicating a gene in idiopathic ASD, it will be listed as "#S" (e.g., 2S, 3S, etc.). If there is no such independent evidence, the gene will be listed simply as "S."

Krishnan Probability Score

Score 0.56626498789177

Ranking 1217/25841 scored genes


[Show Scoring Methodology]
Krishnan and colleagues generated probability scores genome-wide by using a machine learning approach on a human brain-specific gene network. The method was first presented in Nat Neurosci 19, 1454-1462 (2016), and scores for more than 25,000 RefSeq genes can be accessed in column G of supplementary table 3 (see: http://www.nature.com/neuro/journal/v19/n11/extref/nn.4353-S5.xlsx). A searchable browser, with the ability to view networks of associated ASD risk genes, can be found at asd.princeton.edu.
Original Source
Sanders TADA Score

Score 0.93403255719302

Ranking 12446/18665 scored genes


[Show Scoring Methodology]
The TADA score ('Transmission and De novo Association') was introduced by He et al. PLoS Genet 9(8):e1003671 (2013), and is a statistic that integrates evidence from both de novo and transmitted mutations. It forms the basis for the claim of 65 individual genes being strongly associated with autism risk at a false discovery rate of 0.1 (Sanders et al. Neuron 87, 1215-1233 (2015)). The calculated TADA score for 18,665 RefSeq genes can be found in column P of Supplementary Table 6 in the Sanders et al. paper (the column headed 'tadaFdrAscSscExomeSscAgpSmallDel'), which represents a combined analysis of exome data and small de novo deletions (see www.cell.com/cms/attachment/2038545319/2052606711/mmc7.xlsx).
Original Source
Zhang D Score

Score 0.4192843670419

Ranking 1245/20870 scored genes


[Show Scoring Methodology]
The DAMAGES score (disease-associated mutation analysis using gene expression signatures), or D score, was developed to combine evidence from de novo loss-of- function mutation with evidence from cell-type- specific gene expression in the mouse brain (specifically translational profiles of 24 specific mouse CNS cell types isolated from 6 different brain regions). Genes with positive D scores are more likely to be associated with autism risk, with higher-confidence genes having higher D scores. This statistic was first presented by Zhang & Shen (Hum Mutat 38, 204- 215 (2017), and D scores for more than 20,000 RefSeq genes can be found in column M in supplementary table 2 from that paper.
Original Source
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