Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV001849035 | SCV002104457 | likely pathogenic | not provided | 2023-06-22 | criteria provided, single submitter | clinical testing | Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 32504085, 33040083, 30690203, 29727687, 33119769) |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000664416 | SCV002600459 | likely pathogenic | Pontocerebellar hypoplasia, type 1D | 2022-10-12 | criteria provided, single submitter | clinical testing | Variant summary: EXOSC9 c.481C>T (p.Arg161X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant allele was found at a frequency of 2e-05 in 251018 control chromosomes (gnomAD). c.481C>T has been reported in the literature in at least one compound heterozygous individual affected with Spinal Motor Neuronopathy (Burns_2018). This data does not allow any conclusion about variant significance. Additional Western blot analysis using muscle extracts from this same compound heterozygous individual showed that there was severe reduction in EXOSC9 protein (Burns_2018). Two ClinVar submitters have assessed the variant since 2014: one classified the variant as likely pathogenic, and one as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Labcorp Genetics |
RCV001849035 | SCV003459791 | pathogenic | not provided | 2023-10-05 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Arg161*) in the EXOSC9 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in EXOSC9 are known to be pathogenic (PMID: 29727687, 33040083). This variant is present in population databases (rs372318863, gnomAD 0.03%). This premature translational stop signal has been observed in individual(s) with clinical features of pontocerebellar hypoplasia (PMID: 29727687). ClinVar contains an entry for this variant (Variation ID: 549846). For these reasons, this variant has been classified as Pathogenic. |
| OMIM | RCV000664416 | SCV000788347 | pathogenic | Pontocerebellar hypoplasia, type 1D | 2018-07-27 | no assertion criteria provided | literature only |