Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000578534 | SCV000681125 | pathogenic | not provided | 2021-04-12 | criteria provided, single submitter | clinical testing | Observed with a pathogenic variant in two siblings with bilateral congenital sensorineural hearing loss referred for genetic testing at GeneDx and testing of one parent suggests the variants are likely present on opposite alleles (in trans); Canonical splice site variant predicted to result in a null allele in a gene for which loss-of-function is a known mechanism of disease; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); Has not been previously published as pathogenic or benign to our knowledge |
| Labcorp Genetics |
RCV000578534 | SCV004679021 | likely pathogenic | not provided | 2024-01-25 | criteria provided, single submitter | clinical testing | This sequence change affects an acceptor splice site in intron 1 of the OTOA 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 OTOA are known to be pathogenic (PMID: 11972037). This variant is present in population databases (rs376382794, gnomAD 0.005%). Disruption of this splice site has been observed in individual(s) with congenital bilateral deafness (Invitae). ClinVar contains an entry for this variant (Variation ID: 489139). 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. |