Submissions for variant NM_025137.4(SPG11):c.6013G>A (p.Gly2005Ser)

gnomAD frequency: 0.00002  dbSNP: rs776764189

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV001848197	SCV002105742	uncertain significance	Hereditary spastic paraplegia	2020-02-01	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV002034746	SCV002124742	uncertain significance	Hereditary spastic paraplegia 11	2021-07-11	criteria provided, single submitter	clinical testing	This sequence change replaces glycine with serine at codon 2005 of the SPG11 protein (p.Gly2005Ser). The glycine residue is moderately conserved and there is a small physicochemical difference between glycine and serine. This variant is present in population databases (rs776764189, ExAC 0.02%). This variant has not been reported in the literature in individuals affected with SPG11-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Genome-Nilou Lab	RCV002468337	SCV002763769	uncertain significance	Amyotrophic lateral sclerosis type 5		criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV002468338	SCV002763770	uncertain significance	Charcot-Marie-Tooth disease axonal type 2X		criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV002034746	SCV002763771	uncertain significance	Hereditary spastic paraplegia 11		criteria provided, single submitter	clinical testing