rs76461792
Positions:
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_001292063.2(OTOG):c.7631G>A(p.Arg2544Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0041 in 1,549,308 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.0031 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0042 ( 20 hom. )
Consequence
OTOG
NM_001292063.2 missense
NM_001292063.2 missense
Scores
1
5
13
Clinical Significance
Conservation
PhyloP100: 3.90
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 -9 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.008668214).
BP6
?
Variant 11-17635125-G-A is Benign according to our data. Variant chr11-17635125-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 227796.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=5, Uncertain_significance=1}. Variant chr11-17635125-G-A is described in Lovd as [Likely_benign].
BS2
?
High Homozygotes in GnomAdExome4 at 20 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
OTOG | NM_001292063.2 | c.7631G>A | p.Arg2544Gln | missense_variant | 46/56 | ENST00000399397.6 | |
OTOG | NM_001277269.2 | c.7667G>A | p.Arg2556Gln | missense_variant | 45/55 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
OTOG | ENST00000399397.6 | c.7631G>A | p.Arg2544Gln | missense_variant | 46/56 | 5 | NM_001292063.2 | P2 | |
OTOG | ENST00000399391.7 | c.7667G>A | p.Arg2556Gln | missense_variant | 45/55 | 5 | A2 | ||
OTOG | ENST00000342528.2 | n.4606-485G>A | intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00306 AC: 466AN: 152074Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00276 AC: 391AN: 141822Hom.: 4 AF XY: 0.00311 AC XY: 239AN XY: 76834
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GnomAD4 exome AF: 0.00422 AC: 5890AN: 1397114Hom.: 20 Cov.: 33 AF XY: 0.00410 AC XY: 2828AN XY: 689058
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GnomAD4 genome ? AF: 0.00308 AC: 468AN: 152194Hom.: 0 Cov.: 32 AF XY: 0.00286 AC XY: 213AN XY: 74412
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:5
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Benign:3
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 23, 2023 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Feb 01, 2023 | OTOG: BP4, BS2 - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 22, 2021 | - - |
not specified Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jan 20, 2017 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jun 06, 2017 | p.Arg2556Gln in exon 45 of OTOG: This variant is not expected to have clinical s ignificance because it has been identified in 0.5% (292/61730) of European chrom osomes, including 1 homozygote, by the Genome Aggregation Database (gnomAD, http ://gnomad.broadinstitute.org; dbSNP rs76461792). - |
Meniere disease Uncertain:1
Uncertain significance, criteria provided, single submitter | case-control | Otology & Neurotology- Genomics of vestibular disorders (CTS-495), Jose Antonio López Escámez, Centro Pfizer - Universidad de Granada - Junta de Andalucía de Genómica e Investigación Oncológica (GENYO) | Jan 01, 2020 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Pathogenic
DEOGEN2
Benign
T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.
MutationTaster
Benign
D;D;D
PrimateAI
Benign
T
PROVEAN
Uncertain
D;.
REVEL
Benign
Sift
Benign
T;.
Sift4G
Benign
T;T
Vest4
MVP
ClinPred
T
GERP RS
Varity_R
gMVP
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