ClinVar Miner

Submissions for variant NM_001378609.3(OTOGL):c.1890-1G>T

gnomAD frequency: 0.00001  dbSNP: rs777911261
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000498481 SCV000589682 likely pathogenic not provided 2017-06-12 criteria provided, single submitter clinical testing The c.1863-1G>T variant in the OTOGL gene has been reported previously in an individual with autism spectrum disorder who also harbored the R1808X variant in the OTOGL gene, however, familial segregation information and additional clinical information were not included (Lim et al., 2013). The c.1863-1G>T splice site variant destroys the canonical splice acceptor site in intron 17. It is predicted to cause abnormal gene splicing, either leading to an abnormal message that is subject to nonsense-mediated mRNA decay, or to an abnormal protein product if the message is used for protein translation. The c.1863-1G>T variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). We interpret c.1863-1G>T as a likely pathogenic variant.
Fulgent Genetics, Fulgent Genetics RCV002481580 SCV002784577 likely pathogenic Autosomal recessive nonsyndromic hearing loss 84B 2021-08-25 criteria provided, single submitter clinical testing
Invitae RCV000498481 SCV004271424 likely pathogenic not provided 2023-12-20 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 17 of the OTOGL gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in OTOGL are known to be pathogenic (PMID: 23122586). This variant is present in population databases (rs777911261, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with OTOGL-related conditions. ClinVar contains an entry for this variant (Variation ID: 432016). 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 currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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