Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000599015 | SCV000710709 | likely pathogenic | not provided | 2018-02-16 | criteria provided, single submitter | clinical testing | The c.2809+2T>A splice site variant in the USH2A gene has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. This variant destroys the canonical splice donor site in intron 13, and is expected to cause abnormal gene splicing. This variant is not observed in large population cohorts (Lek et al., 2016). Based on currently available evidence, we consider c.2809+2T>A to be a likely pathogenic variant. |
| Laboratory for Molecular Medicine, |
RCV000605844 | SCV000731690 | pathogenic | Rare genetic deafness | 2017-06-20 | criteria provided, single submitter | clinical testing | The c.2809+2T>A variant in USH2A has not been previously reported in individuals with hearing loss or Usher syndrome and is absent from large population databas es. This variant occurs in the invariant region (+/- 1,2) of the splice consensu s sequence and is predicted to cause altered splicing leading to an abnormal or absent protein. Loss of function is an established disease mechanism for autosom al recessive Usher syndrome. In summary, the c.2809+2T>A variant meets criteria to be classified as pathogenic for autosomal recessive Usher syndrome based on the predicted impact to splicing. |
| Labcorp Genetics |
RCV000599015 | SCV001396971 | pathogenic | not provided | 2022-10-28 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. 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: 504388). Disruption of this splice site has been observed in individual(s) with Usher syndrome (PMID: 24944099, 26969326). This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 13 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). |
| Genome- |
RCV003446171 | SCV004172175 | likely pathogenic | Usher syndrome type 2A | 2023-04-11 | criteria provided, single submitter | clinical testing |