Submissions for variant NM_014844.5(TECPR2):c.571C>T (p.Gln191Ter)

dbSNP: rs1888974364

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Institute of Human Genetics, University of Leipzig Medical Center	RCV001257142	SCV001432484	likely pathogenic	Hereditary spastic paraplegia 49	2020-09-16	criteria provided, single submitter	research	This homozygous variant was identified by research trio-exome sequencing in a 1.6 year old girl with global developmental delay, seizures, neonatal hypotonia, gastroesophageal reflux disease, opisthotonus, alacrima, microcephaly, hypoplasia of the corpus callosum and cerebellar vermis atrophy in cranial MRI (published as 09DG00835 in PMID 28940097). The parents were consanguineous (first-degree cousins). Both parents were heterozygous carriers for this variant. This frameshift variant c.571C>T, p.(Gln191*) in exon 5/20 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).
Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center	RCV001257142	SCV004804700	pathogenic	Hereditary spastic paraplegia 49	2024-03-17	criteria provided, single submitter	research