chr19-45940559-CA-C
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1_StrongPM2PP5_Moderate
The NM_002516.4(NOVA2):c.782del(p.Val261GlyfsTer135) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Genomes: not found (cov: 34)
Consequence
NOVA2
NM_002516.4 frameshift
NM_002516.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 8.07
Genes affected
NOVA2 (HGNC:7887): (NOVA alternative splicing regulator 2) Enables sequence-specific mRNA binding activity. Involved in neuron differentiation and regulation of alternative mRNA splicing, via spliceosome. Predicted to be active in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
PVS1
?
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.471 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 19-45940559-CA-C is Pathogenic according to our data. Variant chr19-45940559-CA-C is described in ClinVar as [Pathogenic]. Clinvar id is 812085.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-45940559-CA-C is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NOVA2 | NM_002516.4 | c.782del | p.Val261GlyfsTer135 | frameshift_variant | 4/4 | ENST00000263257.6 | |
NOVA2 | XM_006723230.4 | c.455del | p.Val152GlyfsTer135 | frameshift_variant | 5/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NOVA2 | ENST00000263257.6 | c.782del | p.Val261GlyfsTer135 | frameshift_variant | 4/4 | 1 | NM_002516.4 | P1 | |
NOVA2 | ENST00000676183.1 | c.974del | p.Val325GlyfsTer135 | frameshift_variant | 4/4 |
Frequencies
GnomAD3 genomes ? Cov.: 34
GnomAD3 genomes
?
Cov.:
34
GnomAD4 exome Cov.: 61
GnomAD4 exome
Cov.:
61
GnomAD4 genome ? Cov.: 34
GnomAD4 genome
?
Cov.:
34
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Neurodevelopmental disorder with or without autistic features and/or structural brain abnormalities Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Apr 30, 2020 | - - |
Intellectual disability, severe Pathogenic:1
Pathogenic, criteria provided, single submitter | research | Diagnostic Laboratory, Strasbourg University Hospital | Sep 26, 2019 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at