Submissions for variant NM_025137.4(SPG11):c.6864_6866dup (p.Ala2288_Gln2289insHis)

gnomAD frequency: 0.00003  dbSNP: rs1331704584

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000792737	SCV000932051	uncertain significance	Hereditary spastic paraplegia 11	2022-09-27	criteria provided, single submitter	clinical testing	This variant, c.6864_6866dup, results in the insertion of 1 amino acid(s) of the SPG11 protein (p.Ala2288_Gln2289insHis), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (no rsID available, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with SPG11-related conditions. ClinVar contains an entry for this variant (Variation ID: 639830). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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 Diagnostics Laboratory, The Hospital for Sick Children	RCV001849095	SCV002105767	uncertain significance	Hereditary spastic paraplegia	2019-04-01	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002370066	SCV002667597	uncertain significance	Inborn genetic diseases	2020-08-21	criteria provided, single submitter	clinical testing	The c.6864_6866dupCCA variant (also known as p.A2288_Q2289insH), located in coding exon 38 of the SPG11 gene, results from an in-frame insertion of CCA due to the duplication of nucleotides 6864 through 6866. This results in the insertion of an extra residue (H) between codons 2288 and 2289. This amino acid region is not well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Genome-Nilou Lab	RCV002468050	SCV002763658	uncertain significance	Amyotrophic lateral sclerosis type 5		criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV002468051	SCV002763659	uncertain significance	Charcot-Marie-Tooth disease axonal type 2X		criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000792737	SCV002763660	uncertain significance	Hereditary spastic paraplegia 11		criteria provided, single submitter	clinical testing