Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Institute of Human Genetics, |
RCV001250479 | SCV001386723 | uncertain significance | Hereditary spastic paraplegia 49 | 2020-07-11 | criteria provided, single submitter | curation | This variant has been reported compound heterozygous with the pathogenic variant c.1319del, p.(Leu440Argfs*19) in one individual from Ashkenazi Jewish descent (PMID: 26542466). He displayed developmental delay, muscular hypotonia, gait ataxia and symptoms of autonomic neuropathy. The variant is paternally inherited. This missense variant c.566C>T, p.(Thr189Ile) in exon 4/20 of TECPR2 has not been reported in the general population (gnomAD), in public mutation databases or in the literature. 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). Multiple in silico-tools predict this variant as damaging. Taken together, we classify this variant as of unknown significance based on the ACMG recommendations (Richards et al., 2015, PMID 25741868; criteria: PM2 PM3 PP3). |
OMIM | RCV001250479 | SCV001890896 | pathogenic | Hereditary spastic paraplegia 49 | 2021-09-15 | no assertion criteria provided | literature only |