Submissions for variant NM_003119.4(SPG7):c.220G>A (p.Gly74Arg)

gnomAD frequency: 0.00022  dbSNP: rs114854791

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000198775	SCV000252326	uncertain significance	not provided	2014-04-25	criteria provided, single submitter	clinical testing	p.Gly74Arg (GGG>AGG): c.220 G>A in exon 2 of the SPG7 gene (NM_003119.2). A variant of unknown significance has been identified in the SPG7 gene. The G74R variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The G74R variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is mostly conserved across species; although, Arginine is present at this position in another species. In silico analysis predicts this variant is probably damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. The variant is found in MITONUC-MITOP panel(s).
Fulgent Genetics, Fulgent Genetics	RCV000765319	SCV000896578	uncertain significance	Hereditary spastic paraplegia 7	2018-10-31	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000765319	SCV001484517	likely benign	Hereditary spastic paraplegia 7	2023-04-24	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV001847887	SCV002105875	uncertain significance	Hereditary spastic paraplegia	2016-12-12	criteria provided, single submitter	clinical testing
Athena Diagnostics	RCV000198775	SCV002770736	uncertain significance	not provided	2022-04-13	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003993885	SCV004813964	uncertain significance	not specified	2024-02-28	criteria provided, single submitter	clinical testing	Variant summary: SPG7 c.220G>A (p.Gly74Arg) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.0001 in 251020 control chromosomes. To our knowledge, no occurrence of c.220G>A in individuals affected with Hereditary Spastic Paraplegia 7 and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 215213). Based on the evidence outlined above, the variant was classified as uncertain significance.