Submissions for variant NM_003119.4(SPG7):c.739C>T (p.Arg247Ter)

gnomAD frequency: 0.00001  dbSNP: rs779055639

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001220525	SCV001392520	pathogenic	Hereditary spastic paraplegia 7	2023-11-27	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Arg247*) in the SPG7 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SPG7 are known to be pathogenic (PMID: 21623769, 22964162). This variant is present in population databases (rs779055639, gnomAD 0.01%). This premature translational stop signal has been observed in individual(s) with hereditary spastic paraplegia (PMID: 21623769). ClinVar contains an entry for this variant (Variation ID: 949128). For these reasons, this variant has been classified as Pathogenic.
Genetic Services Laboratory, University of Chicago	RCV001819912	SCV002064530	pathogenic	not provided	2019-01-08	criteria provided, single submitter	clinical testing	DNA sequence analysis of the SPG7 gene demonstrated a sequence change, c.739C>T, which results in the creation of a premature stop codon at amino acid position 247, p.Arg247*. This pathogenic sequence change is predicted to result in an abnormal transcript, which may be degraded, or may lead to the production of a truncated SPG7 protein with potentially abnormal function. This sequence change has been described in the gnomAD database with a low population frequency of 0.0022% (rs779055639). This sequence change has previously been described in a patient with spastic paraplegia in the compound heterozygous state with a missense pathogenic variant (Schlipf et al., 2011).
Fulgent Genetics, Fulgent Genetics	RCV001220525	SCV002807925	pathogenic	Hereditary spastic paraplegia 7	2021-11-29	criteria provided, single submitter	clinical testing
GeneDx	RCV001819912	SCV004168302	pathogenic	not provided	2023-05-11	criteria provided, single submitter	clinical testing	Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 25525159, 30683863, 21623769, 34758253)
PROSPAX: an integrated multimodal progression chart in spastic ataxias, Center for Neurology; Hertie-Institute for Clinical Brain Research	RCV001220525	SCV005061886	pathogenic	Hereditary spastic paraplegia 7	2022-01-01	criteria provided, single submitter	research
Genomics England Pilot Project, Genomics England	RCV001220525	SCV001760387	pathogenic	Hereditary spastic paraplegia 7		no assertion criteria provided	clinical testing