Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001389353 | SCV001590679 | pathogenic | not provided | 2023-06-20 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Arg2673*) in the HSPG2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in HSPG2 are known to be pathogenic (PMID: 11279527, 16927315, 20542149, 23836246). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 1075683). This variant has not been reported in the literature in individuals affected with HSPG2-related conditions. This variant is present in population databases (rs745338204, gnomAD 0.003%). |
| ARUP Laboratories, |
RCV001389353 | SCV002048682 | likely pathogenic | not provided | 2021-03-20 | criteria provided, single submitter | clinical testing | The HSPG2 c.8017C>T; p.Arg2673Ter variant (rs745338204), to our knowledge, is not reported in the medical literature or gene-specific databases. This variant is found on only four chromosomes (4/269232 alleles) in the Genome Aggregation Database. This variant induces an early termination codon and is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. HSPG2 loss-of-function is a known mechanism of disease, and truncating variants downstream of p.Arg2673Ter have been reported in individuals with HSPG2-associated skeletal dysplasias (Arikawa-Hirasawa 2001, Stum 2006). Based on available information, the p.Arg2673Ter variant is considered to be likely pathogenic. References: Arikawa-Hirasawa E et al. Dyssegmental dysplasia, Silverman-Handmaker type, is caused by functional null mutations of the perlecan gene. Nat Genet. 2001 Apr;27(4):431-4. Stum M et al. Spectrum of HSPG2 (Perlecan) mutations in patients with Schwartz-Jampel syndrome. Hum Mutat. 2006 Nov;27(11):1082-91. |