ClinVar Miner

Submissions for variant NM_001292063.2(OTOG):c.292+4A>C

gnomAD frequency: 0.00021  dbSNP: rs535970426
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000766727 SCV000590033 uncertain significance not provided 2023-09-25 criteria provided, single submitter clinical testing In silico analysis supports a deleterious effect on splicing; Has not been previously published as pathogenic or benign to our knowledge
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000497858 SCV000731754 uncertain significance not specified 2017-07-25 criteria provided, single submitter clinical testing The c.328+4A>C variant in OTOG has not been previously reported in individuals w ith hearing loss, but has been identified in 10/24674 of Latino chromosomes and 17/66944 of European chromosomes by the Genome Aggregation Database (gnomAD, htt p://gnomad.broadinstitute.org/; dbSNP rs535970426). Although this variant has be en seen in the general population, its frequency is low enough to be consistent with a recessive carrier frequency. This variant is located in the 5' splice reg ion. Computational tools suggest a possible impact to splicing. However, this in formation is not predictive enough to determine out pathogenicity. In summary, t he clinical significance of the c.328+4A>C variant is uncertain.
Fulgent Genetics, Fulgent Genetics RCV002489217 SCV002790440 uncertain significance Autosomal recessive nonsyndromic hearing loss 18B 2021-09-08 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000766727 SCV003452409 uncertain significance not provided 2022-08-10 criteria provided, single submitter clinical testing 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. 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. ClinVar contains an entry for this variant (Variation ID: 432317). This variant has not been reported in the literature in individuals affected with OTOG-related conditions. This variant is present in population databases (rs535970426, gnomAD 0.04%). This sequence change falls in intron 3 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.

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