Submissions for variant NM_014844.5(TECPR2):c.2998G>T (p.Asp1000Tyr)

dbSNP: rs1889962674

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Institute of Human Genetics, University of Leipzig Medical Center	RCV001249187	SCV001365392	uncertain significance	Hereditary spastic paraplegia 49	2020-06-27	criteria provided, single submitter	research	This homozygous variant was identified by quattro exome sequencing in a 5 year old boy with developmental delay followed by intellectual disability, muscular hypotonia, ataxia, hearing loss and recurrent pulmonary infections. The parents were consanguineous. Both parents were heterozygous carriers for this variant. One similarly affected younger brother was confirmed to carry the variant also homozygous. This missense variant c.2998G>T, p.(Asp1000Tyr) in exon 13/20 of TECPR2 has not been reported in the general population, in public mutation databases or in the literature. However, 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 PP3).
Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center	RCV001249187	SCV004807882	uncertain significance	Hereditary spastic paraplegia 49	2024-03-23	criteria provided, single submitter	clinical testing
OMIM	RCV001249187	SCV001981627	pathogenic	Hereditary spastic paraplegia 49	2021-10-19	no assertion criteria provided	literature only