Submissions for variant NM_025137.4(SPG11):c.7115T>A (p.Leu2372Ter)

gnomAD frequency: 0.00001  dbSNP: rs762984907

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000196229	SCV000253722	pathogenic	Hereditary spastic paraplegia 11	2022-10-03	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the SPG11 protein in which other variant(s) (p.His2388Thrfs*6) have been determined to be pathogenic (Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 216009). This premature translational stop signal has been observed in individual(s) with hereditary spastic paraplegia (PMID: 27217339). This variant is present in population databases (rs762984907, gnomAD 0.0009%). This sequence change creates a premature translational stop signal (p.Leu2372*) in the SPG11 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 72 amino acid(s) of the SPG11 protein.
Mayo Clinic Laboratories, Mayo Clinic	RCV004791320	SCV005414257	likely pathogenic	not provided	2023-10-23	criteria provided, single submitter	clinical testing	PM2_moderate, PM3_strong, PVS1_moderate