Submissions for variant NM_025137.4(SPG11):c.7150A>T (p.Lys2384Ter)

gnomAD frequency: 0.00001  dbSNP: rs1555446078

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000535276	SCV000642283	pathogenic	Hereditary spastic paraplegia 11	2022-11-01	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Lys2384*) in the SPG11 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 60 amino acid(s) of the SPG11 protein. This variant is not present in population databases (gnomAD no frequency). 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: 466567). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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. For these reasons, this variant has been classified as Pathogenic.
Neurometabolic Diseases Laboratory, Bellvitge Biomedical Research Institute (IDIBELL)	RCV000535276	SCV003920824	likely pathogenic	Hereditary spastic paraplegia 11	2023-04-27	criteria provided, single submitter	research