Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Baylor Genetics | RCV000169353 | SCV001162995 | pathogenic | Rhizomelic chondrodysplasia punctata type 1 | criteria provided, single submitter | clinical testing | ||
Invitae | RCV001068245 | SCV001233344 | pathogenic | Peroxisome biogenesis disorder 9B | 2023-10-05 | criteria provided, single submitter | clinical testing | 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). This variant is present in population databases (rs267608254, gnomAD 0.009%). Disruption of this splice site has been observed in individuals with rhizomelic chondrodysplasia punctata (PMID: 12325024). This variant is also known as IVS2+1G>C. ClinVar contains an entry for this variant (Variation ID: 188975). Studies have shown that disruption of this splice site alters PEX7 gene expression (PMID: 12325024). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000169353 | SCV001442631 | pathogenic | Rhizomelic chondrodysplasia punctata type 1 | 2020-10-12 | criteria provided, single submitter | clinical testing | Variant summary: PEX7 c.188+1G>C (also known as IVS2+1G>C) 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. At-least one in-silico prediction tool, Transcript-inferred Pathogenicity score (TraP), predicts a possible pathogenic outcome for this variant. The variant allele was found at a frequency of 1.2e-05 in 251450 control chromosomes (gnomAD). c.188+1G>C has been reported in the literature in individuals affected with Rhizomelic Chondrodysplasia Punctata Type 1 (e.g. Braverman_2002). These data indicate that the variant is likely to be associated with disease. A ClinVar submitter (evaluation after 2014) cites the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
Myriad Genetics, |
RCV000169353 | SCV002060195 | likely pathogenic | Rhizomelic chondrodysplasia punctata type 1 | 2021-10-27 | criteria provided, single submitter | clinical testing | NM_000288.3(PEX7):c.188+1G>C is a canonical splice variant classified as likely pathogenic in the context of rhizomelic chondrodysplasia punctata type 1. c.188+1G>C has been observed in a case with relevant disease (PMID: 12325024). Functional assessments of this variant are not available in the literature. c.188+1G>C has been observed in population frequency databases (gnomAD: AMR 0.01%). In summary, NM_000288.3(PEX7):c.188+1G>C is a canonical splice variant in a gene where loss of function is a known mechanism of disease, is predicted to disrupt protein function, and has been observed more frequently in cases with the relevant disease than in healthy populations. Please note: this variant was assessed in the context of healthy population screening. |
Fulgent Genetics, |
RCV002485052 | SCV002796244 | pathogenic | Phytanic acid storage disease; Rhizomelic chondrodysplasia punctata type 1; Peroxisome biogenesis disorder 9B | 2022-01-19 | criteria provided, single submitter | clinical testing | |
Gene |
RCV003233479 | SCV003930843 | pathogenic | not provided | 2023-06-09 | criteria provided, single submitter | clinical testing | Canonical splice site variant predicted to result in a null allele in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 25525159, 31589614, 31964843, 12325024) |
Baylor Genetics | RCV001068245 | SCV004203910 | pathogenic | Peroxisome biogenesis disorder 9B | 2023-05-25 | criteria provided, single submitter | clinical testing |