Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001056217 | SCV001220645 | likely pathogenic | Werner syndrome | 2024-01-24 | criteria provided, single submitter | clinical testing | This sequence change affects a donor splice site in intron 4 of the WRN gene. RNA analysis indicates that disruption of this splice site induces altered splicing and may result in an absent or disrupted protein product. This variant is present in population databases (rs775196937, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with WRN-related conditions. ClinVar contains an entry for this variant (Variation ID: 851757). Studies have shown that disruption of this splice site results in skipping of exon 4 and introduces a premature termination codon (Invitae). The resulting mRNA is expected to undergo nonsense-mediated decay. 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. |
Baylor Genetics | RCV001056217 | SCV004208892 | likely pathogenic | Werner syndrome | 2022-10-28 | criteria provided, single submitter | clinical testing |