19-45940515-AG-A
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PVS1_StrongPM2PP5
The NM_002516.4(NOVA2):c.826del(p.Leu276CysfsTer120) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (no stars).
Frequency
Genomes: not found (cov: 34)
Consequence
NOVA2
NM_002516.4 frameshift
NM_002516.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 6.00
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 7 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 0.442 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 19-45940515-AG-A is Pathogenic according to our data. Variant chr19-45940515-AG-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 1326304.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr19-45940515-AG-A is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NOVA2 | NM_002516.4 | c.826del | p.Leu276CysfsTer120 | frameshift_variant | 4/4 | ENST00000263257.6 | |
NOVA2 | XM_006723230.4 | c.499del | p.Leu167CysfsTer120 | frameshift_variant | 5/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NOVA2 | ENST00000263257.6 | c.826del | p.Leu276CysfsTer120 | frameshift_variant | 4/4 | 1 | NM_002516.4 | P1 | |
NOVA2 | ENST00000676183.1 | c.1018del | p.Leu340CysfsTer120 | 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: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Neurodevelopmental disorder with or without autistic features and/or structural brain abnormalities Pathogenic:1
Likely pathogenic, no assertion criteria provided | clinical testing | Blueprint Genetics | Nov 17, 2021 | - - |
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
Publications
No publications associated with this variant yet.