8-91071136-A-G
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_016023.5(OTUD6B):c.83-2A>G variant causes a splice acceptor, intron change. The variant allele was found at a frequency of 0.00000137 in 1,459,624 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Consequence
NM_016023.5 splice_acceptor, intron
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
OTUD6B | NM_016023.5 | c.83-2A>G | splice_acceptor_variant, intron_variant | Intron 1 of 6 | ENST00000404789.8 | NP_057107.4 | ||
OTUD6B | NM_001416022.1 | c.83-2A>G | splice_acceptor_variant, intron_variant | Intron 1 of 5 | NP_001402951.1 | |||
OTUD6B | NM_001286745.3 | c.-361-2A>G | splice_acceptor_variant, intron_variant | Intron 1 of 7 | NP_001273674.1 | |||
OTUD6B | XM_047421864.1 | c.83-2A>G | splice_acceptor_variant, intron_variant | Intron 1 of 3 | XP_047277820.1 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1459624Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 726132
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Epilepsy;C0432072:Dysmorphic features;C3714756:Intellectual disability Pathogenic:1
This variant was found in one family, homozygous in 2 affected sibs: one sister is 5yo, severe intellectual disability, epilepsy, microcephaly, hypotonia, mild vetriculomegaly, hypoplastic corpus callosum, dysmorphisms, scoliosis, toe syndactyly. Other sister is 3yo, severe delays, epilepsy, microcephaly, hypotonia, complex CHD, dysmorphisms, toe syndactyly. -
Intellectual developmental disorder with dysmorphic facies, seizures, and distal limb anomalies Pathogenic:1
- -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at