rs753850661
Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7
The NM_001292063.2(OTOG):c.8022G>A(p.Pro2674=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000441 in 1,548,172 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00027 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00046 ( 0 hom. )
Consequence
OTOG
NM_001292063.2 synonymous
NM_001292063.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.30
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 -11 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.9).
BP6
?
Variant 11-17640923-G-A is Benign according to our data. Variant chr11-17640923-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 227803.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-2.3 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
OTOG | NM_001292063.2 | c.8022G>A | p.Pro2674= | synonymous_variant | 51/56 | ENST00000399397.6 | |
OTOG | NM_001277269.2 | c.8058G>A | p.Pro2686= | synonymous_variant | 50/55 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
OTOG | ENST00000399397.6 | c.8022G>A | p.Pro2674= | synonymous_variant | 51/56 | 5 | NM_001292063.2 | P2 | |
OTOG | ENST00000399391.7 | c.8058G>A | p.Pro2686= | synonymous_variant | 50/55 | 5 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.000269 AC: 41AN: 152222Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000255 AC: 37AN: 145142Hom.: 0 AF XY: 0.000319 AC XY: 25AN XY: 78402
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GnomAD4 exome AF: 0.000460 AC: 642AN: 1395950Hom.: 0 Cov.: 34 AF XY: 0.000449 AC XY: 309AN XY: 688590
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GnomAD4 genome ? AF: 0.000269 AC: 41AN: 152222Hom.: 0 Cov.: 32 AF XY: 0.000296 AC XY: 22AN XY: 74360
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ClinVar
Significance: Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | May 12, 2021 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Sep 04, 2023 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jul 16, 2015 | p.Pro2686Pro in exon 50 of OTOG: This variant is not expected to have clinical s ignificance because it does not alter an amino acid residue and is not located w ithin the splice consensus sequence. It has been identified in 6/14424 chromosom es by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org). - |
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