Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000595998 | SCV000709743 | pathogenic | Rare genetic deafness | 2017-04-11 | criteria provided, single submitter | clinical testing | The duplication of exons 57-60 of USH2A has been previously reported in one 66 y ear old female with isolated retinal degeneration (Lenassi 2015). It has also be en reported in 1/32850 European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org). Although this variant has been seen in t he general population, its frequency is low enough to be consistent with a reces sive carrier frequency. Manual breakpoint analysis using NGS data reveals that t he variant is a tandem duplication of exons 57-60, and is predicted to cause a f rameshift leading to a truncated or absent protein. In summary, this variant mee ts criteria to be classified as pathogenic for autosomal recessive Usher syndrom e based on the predicted impact to the protein. |
| Invitae | RCV001031047 | SCV001194353 | pathogenic | not provided | 2022-08-31 | criteria provided, single submitter | clinical testing | This variant results in a copy number gain of the genomic region encompassing exon(s) 57-60 of the USH2A gene. While the exact position of this variant cannot be determined from the data, sub-genic copy number gains are generally in tandem (PMID: 25640679). This variant is predicted to be out-of-frame, and may result in an absent or disrupted protein product. Loss-of-function variants in USH2A are known to be pathogenic (PMID: 10729113, 10909849, 20507924, 25649381). A similar copy number variant has been observed in individuals with USH2A-related conditions (PMID: 25649381, 29655801; Invitae). This variant is also known as 11048-?_11711+?dup. For these reasons, this variant has been classified as Pathogenic. |