rs2023483
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_001292063.2(OTOG):āc.8364G>Cā(p.Leu2788=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.317 in 1,548,636 control chromosomes in the GnomAD database, including 81,754 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Genomes: š 0.35 ( 10263 hom., cov: 33)
Exomes š: 0.31 ( 71491 hom. )
Consequence
OTOG
NM_001292063.2 synonymous
NM_001292063.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -4.72
Genes affected
OTOG (HGNC:8516): (otogelin) The protein encoded by this gene is a component of the acellular membranes of the inner ear. Disruption of the orthologous mouse gene shows that it plays a role in auditory and vestibular functions. It is involved in fibrillar network organization, the anchoring of otoconial membranes and cupulae to the neuroepithelia, and likely in sound stimulation resistance. Mutations in this gene cause autosomal recessive nonsyndromic deafness, type 18B. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, May 2014]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.74).
BP6
?
Variant 11-17642195-G-C is Benign according to our data. Variant chr11-17642195-G-C is described in ClinVar as [Benign]. Clinvar id is 226919.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-17642195-G-C is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=-4.72 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.501 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
OTOG | NM_001292063.2 | c.8364G>C | p.Leu2788= | synonymous_variant | 53/56 | ENST00000399397.6 | |
OTOG | NM_001277269.2 | c.8400G>C | p.Leu2800= | synonymous_variant | 52/55 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
OTOG | ENST00000399397.6 | c.8364G>C | p.Leu2788= | synonymous_variant | 53/56 | 5 | NM_001292063.2 | P2 | |
OTOG | ENST00000399391.7 | c.8400G>C | p.Leu2800= | synonymous_variant | 52/55 | 5 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.352 AC: 53536AN: 151936Hom.: 10241 Cov.: 33
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GnomAD3 exomes AF: 0.295 AC: 43244AN: 146758Hom.: 7109 AF XY: 0.305 AC XY: 24121AN XY: 79088
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GnomAD4 exome AF: 0.314 AC: 437880AN: 1396582Hom.: 71491 Cov.: 37 AF XY: 0.316 AC XY: 217337AN XY: 688682
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GnomAD4 genome ? AF: 0.353 AC: 53605AN: 152054Hom.: 10263 Cov.: 33 AF XY: 0.350 AC XY: 26017AN XY: 74334
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ClinVar
Significance: Benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:4
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Nov 24, 2014 | Leu2800Leu in exon 52 of OTOG: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue and is not located wit hin the splice consensus sequence. It has been identified in 58.8% (114/194) of Luhya (Kenyan) chromosomes from a broad population by the 1000 Genomes Project ( http://www.ncbi.nlm.nih.gov/projects/SNP; dbSNP rs2023483). - |
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | May 09, 2017 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Autosomal recessive nonsyndromic hearing loss 18B Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | May 18, 2021 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at