ClinVar Miner

Submissions for variant NM_001292063.2(OTOG):c.8541+5G>A

gnomAD frequency: 0.00008  dbSNP: rs754883697
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000606159 SCV000712228 uncertain significance not specified 2016-06-21 criteria provided, single submitter clinical testing The c.8577+5G>A variant in OTOG has not been previously reported in individuals with hearing loss. This variant has been identified in 0.4% (1/286) of Latino ch romosomes and in 0.1% (7/7640) of South Asian chromosomes by the Exome Aggregati on Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs754883697). Althoug h this variant has been seen in the general population, its frequency is not hig h enough to rule out a pathogenic role. This variant is located in the 5' splice region. Computational tools do suggest an impact to splicing. However, this inf ormation is not predictive enough to rule out pathogenicity. In summary, the cli nical significance of the c.8577+5G>A variant is uncertain.
GeneDx RCV001584418 SCV001811933 likely pathogenic not provided 2025-01-07 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; Intronic variant directly or indirectly altering the +5 splice site in a gene for which loss of function is a known mechanism of disease, and splice predictors support a deleterious effect
Labcorp Genetics (formerly Invitae), Labcorp RCV001584418 SCV005824868 uncertain significance not provided 2024-07-21 criteria provided, single submitter clinical testing This sequence change falls in intron 54 of the OTOG gene. It does not directly change the encoded amino acid sequence of the OTOG protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs754883697, gnomAD 0.08%). This variant has been observed in individual(s) with clinical features of OTOG-related conditions (Invitae). ClinVar contains an entry for this variant (Variation ID: 505108). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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