Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001751397 | SCV001386597 | likely pathogenic | not provided | 2022-05-12 | criteria provided, single submitter | clinical testing | This sequence change affects an acceptor splice site in intron 2 of the POLE 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 POLE are known to be pathogenic (PMID: 23230001, 25948378, 30503519). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with POLE-related conditions. ClinVar contains an entry for this variant (Variation ID: 944485). 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. |
| Gene |
RCV001751397 | SCV001997375 | uncertain significance | not provided | 2019-12-23 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; Canonical splice site variant predicted to result in an in-frame deletion of exon 3; Not observed in large population cohorts (Lek 2016) |