Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000588951 | SCV000696483 | likely pathogenic | Peroxisome biogenesis disorder | 2022-03-01 | criteria provided, single submitter | clinical testing | Variant summary: PEX6 c.1233+1G>A is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Several computational tools predict a significant impact on normal splicing: Four predict the variant abolishes a 5' prime splicing donor site. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 4e-06 in 251488 control chromosomes (gnomAD). c.1233+1G>A has been reported in a severely affected homozygous infant with a clinical diagnosis of Zellweger Syndrome (Internal data). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Labcorp Genetics |
RCV000588951 | SCV002271807 | likely pathogenic | Peroxisome biogenesis disorder | 2023-09-22 | criteria provided, single submitter | clinical testing | This variant is present in population databases (rs763459576, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with PEX6-related conditions. ClinVar contains an entry for this variant (Variation ID: 495794). 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. This sequence change affects a donor splice site in intron 4 of the PEX6 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 PEX6 are known to be pathogenic (PMID: 10408779, 21031596, 31831025). |
| Baylor Genetics | RCV003471937 | SCV004201587 | likely pathogenic | Heimler syndrome 2 | 2024-03-16 | criteria provided, single submitter | clinical testing | |
| Natera, |
RCV001834834 | SCV002077321 | likely pathogenic | Zellweger spectrum disorders | 2020-11-10 | no assertion criteria provided | clinical testing |