Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001377228 | SCV001574503 | likely pathogenic | Bifunctional peroxisomal enzyme deficiency; Perrault syndrome | 2023-09-27 | criteria provided, single submitter | clinical testing | This sequence change affects a donor splice site in intron 4 of the HSD17B4 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 HSD17B4 are known to be pathogenic (PMID: 11810648, 16385454, 20673864). This variant is present in population databases (rs770772281, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with HSD17B4-related conditions. ClinVar contains an entry for this variant (Variation ID: 1066269). 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 |
RCV001581112 | SCV001812065 | likely pathogenic | not provided | 2019-08-19 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); Canonical splice site variant predicted to result in an in-frame deletion of a critical region |
Baylor Genetics | RCV001826124 | SCV004192423 | pathogenic | Bifunctional peroxisomal enzyme deficiency | 2024-03-13 | criteria provided, single submitter | clinical testing | |
Natera, |
RCV001826124 | SCV002075399 | likely pathogenic | Bifunctional peroxisomal enzyme deficiency | 2020-02-06 | no assertion criteria provided | clinical testing |