Submissions for variant NM_025137.4(SPG11):c.442+5G>T

dbSNP: rs752482400

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics	RCV000984469	SCV000999004	uncertain significance	Hereditary spastic paraplegia 11	2019-09-12	criteria provided, single submitter	clinical testing	A homozygous 5' splice site variation in intron 2 of the SPG11 gene that affects the position 5 nucleotides downstream of donor splice site of exon 2 was detected. The observed variant c.442+5G>T (Splice site) has not been reported in the 1000 genomes and ExAC databases. The in silico prediction of the variant is damaging by MutationTaster2 and DANN. The observed variant has been predicted to result in altered splicing by Human Splicing Finder. The reference base is conserved across species.
Neuberg Supratech Reference Laboratories Pvt Ltd, Neuberg Centre for Genomic Medicine	RCV000984469	SCV004100442	uncertain significance	Hereditary spastic paraplegia 11		criteria provided, single submitter	clinical testing	The splice region variant c.442+5G>T in SPG11 (NM_025137.4) has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. It has been submitted to ClinVar as Uncertain Significance.The c.442+5G>T variant is novel (not in any individuals) in gnomAD Exomes and is novel (not in any individuals) in 1000 Genomes. The c.442+5G>T variant is predicted to disrupt splicing by all splice site algorithms. The nucleotide c.442+5G>T in SPG11 is predicted conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Uncertain Significance.