Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Baylor Genetics | RCV001004177 | SCV001162994 | pathogenic | Rhizomelic chondrodysplasia punctata type 1 | criteria provided, single submitter | clinical testing | ||
| Invitae | RCV002549235 | SCV003317833 | pathogenic | Peroxisome biogenesis disorder 9B | 2022-02-21 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as 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: 813363). Disruption of this splice site has been observed in individuals with clinical features of rhizomelic chondrodysplasia punctata (PMID: 12325024; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 2 of the PEX7 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 PEX7 are known to be pathogenic (PMID: 12325024, 12522768, 20301447). |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001004177 | SCV003800712 | likely pathogenic | Rhizomelic chondrodysplasia punctata type 1 | 2023-01-01 | criteria provided, single submitter | clinical testing | Variant summary: PEX7 c.188+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 canonical 5' splicing donor site. However, these predictions have yet to be confirmed by functional studies. The variant was absent in 251450 control chromosomes. To our knowledge, no occurrence of c.188+1G>A in individuals affected with Rhizomelic Chondrodysplasia Punctata Type 1 and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic. |