Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000826126 | SCV000967636 | likely pathogenic | Peroxisome biogenesis disorder | 2018-08-23 | criteria provided, single submitter | clinical testing | The c.2094+1G>A variant in PEX6 has not been reported in individuals with Zellwe ger spectrum disorder and was absent from large population studies. This variant occurs in the invariant region (+/- 1,2) of the splice consensus sequence and i s predicted to cause altered splicing leading to an abnormal or absent protein. A similar variant affecting this splice site (2094+2T>C) has been identified in an individual with a peroxisomal biogenesis disorder where it was shown to lead to retention of intron 10. Loss of function of the PEX6 gene is an established d isease mechanism in autosomal recessive Zellweger syndrome and other peroxisome biogenesis disorders. In summary, although additional studies are required to fu lly establish its clinical significance, the c.2094+1G>A variant is likely patho genic for Zellweger spectrum disorder. ACMG/AMP Criteria applied: PVS1_Strong. P M2. |
| Invitae | RCV000826126 | SCV002283841 | likely pathogenic | Peroxisome biogenesis disorder | 2021-10-03 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with PEX6-related conditions. 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 667387). This variant is not present in population databases (ExAC no frequency). This sequence change affects a donor splice site in intron 10 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: 8670792, 19877282, 21031596). |
| Baylor Genetics | RCV003473522 | SCV004201566 | likely pathogenic | Heimler syndrome 2 | 2023-05-11 | criteria provided, single submitter | clinical testing |