Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Institute of Human Genetics, |
RCV001290269 | SCV001469093 | likely pathogenic | Hereditary spastic paraplegia 49 | 2021-01-16 | criteria provided, single submitter | clinical testing | This homozygous variant was identified by research trio-genome sequencing (100K Genomes Project) in a 5 year old girl with global developmental delay, broad based gait, muscular hypotonia, feeding difficulties with aspiration, recurrent respiratory infections and dysmorphic ventricles as well as reduction of white matter volume in cranial MRI. The parents were consanguineous (first-degree cousins). Both parents were heterozygous carriers for this variant. This frameshift variant c.694dup, p.(Thr232Asnfs*15) in exon 6/20 of TECPR2 has not been reported in the general population. 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). |