NOVA2

NOVA alternative splicing regulator 2

Basic information

Region (hg38): 19:45933734-45974044

Previous symbols: [ "NOVA3" ]

Links

ENSG00000104967 ∙ NCBI:4858 ∙ OMIM:601991 ∙ HGNC:7887 ∙ Uniprot:Q9UNW9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• neurodevelopmental disorder with or without autistic features and/or structural brain abnormalities (Moderate), mode of inheritance: AD
• neurodevelopmental disorder with or without autistic features and/or structural brain abnormalities (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Neurodevelopmental disorder with or without autistic features and/or structural brain abnormalities	AD	General	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	Craniofacial; Neurologic	32197073

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the NOVA2 gene.

• Neurodevelopmental disorder with or without autistic features and/or structural brain abnormalities (4 variants)
• not provided (2 variants)
• Intellectual disability, severe (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NOVA2 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				13	4	17
missense			26	2		28
nonsense			1			1
start loss			1			1
frameshift	5	1				6
inframe indel			3	1		4
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding				1		1
Total	5	1	31	17	4

Variants in NOVA2

This is a list of pathogenic ClinVar variants found in the NOVA2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
19-45939979-G-A			Uncertain significance (May 25, 2024)
19-45940130-ACT-A		NOVA2-related disorder	Uncertain significance (Aug 05, 2024)
19-45940131-C-T		not specified	Uncertain significance (Jan 15, 2024)
19-45940137-G-A		not specified	Uncertain significance (Apr 26, 2024)
19-45940168-C-T			Uncertain significance (Nov 01, 2022)
19-45940184-G-T		NOVA2-related disorder	Likely benign (Apr 26, 2023)
19-45940187-T-A		NOVA2-related disorder	Likely benign (Apr 26, 2023)
19-45940190-A-C		NOVA2-related disorder	Likely benign (Apr 26, 2023)
19-45940193-G-A			Benign (Oct 01, 2023)
19-45940203-G-T		Inborn genetic diseases	Uncertain significance (Aug 15, 2024)
19-45940207-CGCCCCCTCCGCCCGCCCCGCCGCCCGCCCCG-C		NOVA2-related disorder	Likely pathogenic (Mar 03, 2023)
19-45940211-C-G		NOVA2-related disorder	Likely benign (Dec 01, 2022)
19-45940221-G-C		Inborn genetic diseases	Uncertain significance (Oct 06, 2021)
19-45940243-C-G		Inborn genetic diseases	Uncertain significance (Sep 20, 2023)
19-45940255-T-A			Uncertain significance (Apr 12, 2024)
19-45940299-G-GGGGGCGGCGGC			Uncertain significance (Apr 19, 2024)
19-45940301-G-GGGC			Uncertain significance (Apr 17, 2024)
19-45940342-C-T		Inborn genetic diseases • NOVA2-related disorder	Uncertain significance (Apr 13, 2022)
19-45940351-C-T			Uncertain significance (May 01, 2024)
19-45940354-AG-A		Neurodevelopmental disorder with or without autistic features and/or structural brain abnormalities	Pathogenic (May 06, 2022)
19-45940362-A-G			Uncertain significance (Jan 25, 2024)
19-45940369-TGGC-T		NOVA2-related disorder	Likely benign (Sep 23, 2022)
19-45940394-G-A			Likely benign (Jul 01, 2023)
19-45940439-G-A		not specified	Likely benign (Oct 08, 2024)
19-45940456-G-C		not specified	Uncertain significance (Oct 31, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NOVA2	protein_coding	protein_coding	ENST00000263257	4	39813

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.983	0.0174	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	4.35	70	272	0.258	0.0000188	3065
Missense in Polyphen		5	43.214	0.1157		377
Synonymous	2.88	96	139	0.690	0.0000113	1115
Loss of Function	3.25	0	12.3	0.00	6.16e-7	149

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May regulate RNA splicing or metabolism in a specific subset of developing neurons (By similarity). Binds single strand RNA. {ECO:0000250}.

Intolerance Scores

• rvis_EVS: -0.21
• rvis_percentile_EVS: 38.28

Haploinsufficiency Scores

• pHI: 0.425
• ghis: 0.696

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.201

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Nova2
• Phenotype: nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span)

Gene ontology

• Biological process: mRNA splicing, via spliceosome;regulation of RNA metabolic process;negative regulation of cold-induced thermogenesis
• Cellular component: nucleus
• Molecular function: RNA binding