rs539684481
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_001292063.2(OTOG):c.8322C>A(p.Cys2774Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000143 in 1,396,186 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. C2774C) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_001292063.2 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
OTOG | NM_001292063.2 | c.8322C>A | p.Cys2774Ter | stop_gained | 53/56 | ENST00000399397.6 | |
OTOG | NM_001277269.2 | c.8358C>A | p.Cys2786Ter | stop_gained | 52/55 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
OTOG | ENST00000399397.6 | c.8322C>A | p.Cys2774Ter | stop_gained | 53/56 | 5 | NM_001292063.2 | P2 | |
OTOG | ENST00000399391.7 | c.8358C>A | p.Cys2786Ter | stop_gained | 52/55 | 5 | A2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.0000205 AC: 3AN: 146666Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 78974
GnomAD4 exome AF: 0.00000143 AC: 2AN: 1396186Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 688392
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
OTOG-related disorder Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 14, 2023 | The OTOG c.8358C>A variant is predicted to result in premature protein termination (p.Cys2786*). To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.019% of alleles in individuals of East Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/11-17663700-C-A). Nonsense variants in OTOG are expected to be pathogenic. This variant is interpreted as likely pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at