Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
SIB Swiss Institute of Bioinformatics | RCV000034370 | SCV000930085 | pathogenic | Hereditary spastic paraplegia 46 | 2019-01-25 | criteria provided, single submitter | curation | This variant is interpreted as a Pathogenic for Spastic paraplegia 46, autosomal recessive. The following ACMG Tag(s) were applied: PM2 : Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium. PS3-Moderate : PS3 downgraded in strength to Moderate (PMID:26220345). PVS1 : Predicted nullvariant in a gene where LOF is a known mechanism of disease. PP1 : Cosegregation with disease in multiple affected family members in a gene definitively known to cause the disease (PMID:23332917). |
Institute of Medical Genetics and Applied Genomics, |
RCV001268639 | SCV001447712 | pathogenic | not provided | 2020-10-23 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV005055533 | SCV005720678 | pathogenic | Spastic paraplegia | 2024-04-16 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Arg234*) in the GBA2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in GBA2 are known to be pathogenic (PMID: 23332916, 23332917). This variant is present in population databases (rs398123013, gnomAD 0.01%). This premature translational stop signal has been observed in individual(s) with hereditary spastic paraplegia (PMID: 23332916). ClinVar contains an entry for this variant (Variation ID: 41486). 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. |
OMIM | RCV000034370 | SCV000058354 | pathogenic | Hereditary spastic paraplegia 46 | 2013-02-07 | no assertion criteria provided | literature only | |
Solve- |
RCV000034370 | SCV005091426 | likely pathogenic | Hereditary spastic paraplegia 46 | 2022-06-01 | no assertion criteria provided | provider interpretation | Variant confirmed as disease-causing by referring clinical team |