Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000486199 | SCV000570464 | likely pathogenic | not provided | 2016-05-21 | criteria provided, single submitter | clinical testing | The c.7595-2A>G variant in the USH2A gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This splice site variant destroys the canonical splice acceptor site in intron 40. 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.7595-2A>G variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The c.7595-2A>G variant is a strong candidate for a pathogenic variant, however the possibility it may be a rare benign variant cannot be excluded. |
| Labcorp Genetics |
RCV000486199 | SCV003197097 | likely pathogenic | not provided | 2023-10-26 | criteria provided, single submitter | clinical testing | This sequence change affects an acceptor splice site in intron 40 of the USH2A 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 USH2A are known to be pathogenic (PMID: 10729113, 10909849, 20507924, 25649381). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with USH2A-related conditions. ClinVar contains an entry for this variant (Variation ID: 421305). 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. |
| Genome- |
RCV003446078 | SCV004172073 | likely pathogenic | Usher syndrome type 2A | 2023-04-11 | criteria provided, single submitter | clinical testing | |
| Baylor Genetics | RCV003464018 | SCV004206415 | likely pathogenic | Retinitis pigmentosa 39 | 2022-05-31 | criteria provided, single submitter | clinical testing |