Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000523486 | SCV000619433 | pathogenic | not provided | 2017-07-24 | criteria provided, single submitter | clinical testing | The c.1028_1032delAAGGA variant in the TECPR2 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The c.1028_1032delAAGGA variant causes a frameshift starting with codon Lysine 343, changes this amino acid to an Arginine residue, and creates a premature Stop codon at position 2 of the new reading frame, denoted p.Lys343ArgfsX2. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.1028_1032delAAGGA variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). We interpret c.1028_1032delAAGGA as a pathogenic variant. |
| Institute of Human Genetics, |
RCV001250490 | SCV001387221 | likely pathogenic | Hereditary spastic paraplegia 49 | 2020-07-11 | criteria provided, single submitter | curation | This variant has been reported compound heterozygous with the variant NM_014844.4:c.774del, p.(Asp259Metfs*44) in a girl with developmental delay, muscular hypotonia, gait ataxia, dysarthria and symptoms of autonomic neuropathy (PMID: 32209221). This frameshift variant c.1028_1032del, p.(Lys343Argfs*2) in exon 7/20 of TECPR2 has been previously reported in ClinVar as pathogenic (450814). In the general population the minor allele frequency is 0.000003986 (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). |
| Invitae | RCV001250490 | SCV003316934 | pathogenic | Hereditary spastic paraplegia 49 | 2022-03-31 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Lys343Argfs*2) 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 (no rsID available, gnomAD 0.0009%). This premature translational stop signal has been observed in individual(s) with TECPR2-related conditions (PMID: 32209221). ClinVar contains an entry for this variant (Variation ID: 450814). For these reasons, this variant has been classified as Pathogenic. |
| OMIM | RCV001250490 | SCV001890898 | pathogenic | Hereditary spastic paraplegia 49 | 2021-09-16 | no assertion criteria provided | literature only |