Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001230412 | SCV001402890 | pathogenic | Hereditary spastic paraplegia 49 | 2024-03-18 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Trp1024*) in the TECPR2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TECPR2 are known to be pathogenic (PMID: 23176824, 25590979). This variant is present in population databases (rs765880201, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with TECPR2-related conditions. ClinVar contains an entry for this variant (Variation ID: 957432). For these reasons, this variant has been classified as Pathogenic. |
| Tgen's Center For Rare Childhood Disorders, |
RCV001230412 | SCV001572326 | pathogenic | Hereditary spastic paraplegia 49 | 2021-04-26 | criteria provided, single submitter | research | This variant was identified in a research study as compound heterozygous with the frameshift variant NM_014844.5:c.1318_1319delCT p.(Leu440Valfs*13) in a girl with cerebellar atrophy, central apnea, developmental delay, muscular hypotonia, gait ataxia, and dysarthria. This is a stop_gain variant NM_014844.5:c.3072G>A, p.(Trp1024Ter) in exon 13/20 of TECPR2. In the general population the minor allele frequency is 0.00001195 (gnomAD). Biallelic truncating or missense variants have been described to cause "Spastic paraplegia 49, autosomal recessive" (Oz-Levi et al. Am J Hum Genet. 2012, PMID: 23176824). Taken together, we classify this variant as likely pathogenic based on the ACMG recommendations (Richards et al., 2015, PMID 25741868; criteria: PVS1 PM2). |