Submissions for variant NM_003119.4(SPG7):c.2070del (p.Phe691fs)

dbSNP: rs1555617559

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000627617	SCV000748617	likely pathogenic	not provided	2018-04-16	criteria provided, single submitter	clinical testing	A variant that is likely pathogenic has been identified in the SPG7 gene. The c.2070delC variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The c.2070delC variant causes a frameshift starting with codon Phenylalanine 691, changes this amino acid to a Serine residue, and creates a premature Stop codon at position 8 of the new reading frame, denoted p.Phe691SerfsX8. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.2070delC variant is not observed in large population cohorts (Lek et al., 2016). Therefore, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded.
Paris Brain Institute, Inserm - ICM	RCV001380103	SCV001451065	pathogenic	Hereditary spastic paraplegia 7		criteria provided, single submitter	clinical testing
Invitae	RCV001380103	SCV001578049	pathogenic	Hereditary spastic paraplegia 7	2020-01-24	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in SPG7 are known to be pathogenic (PMID: 21623769, 22964162). This variant has not been reported in the literature in individuals with SPG7-related conditions. ClinVar contains an entry for this variant (Variation ID: 524121). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Phe691Serfs*8) in the SPG7 gene. It is expected to result in an absent or disrupted protein product.