Submissions for variant NM_003119.4(SPG7):c.861dup (p.Asn288Ter)

dbSNP: rs797046003

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genetic Services Laboratory, University of Chicago	RCV000194085	SCV000249018	pathogenic	Hereditary spastic paraplegia 7	2015-07-31	criteria provided, single submitter	clinical testing
GeneDx	RCV000199034	SCV000252335	pathogenic	not provided	2014-07-03	criteria provided, single submitter	clinical testing	c.861dupT: p.Asn288Stop (N288X) in exon 6 of the SPG7 gene (NM_003119.2). The normal sequence with the base that is duplicated in braces is: CTTT{T}gtaa with the exonic bases in upper case and the intronic bases in lower case. The c.861dupT mutation in the SPG7 gene has been reported previously in association with spastic paraplegia in a patient who was compound heterozygous for c.861dupT and a missense mutation in the SPG7 gene. After identification of the SPG7 mutations, this patient was subsequently found to have optic neuropathy (Klebe et al., 2012). The duplication causes the replacement of Asparagine 288 with a premature Stop codon, denoted p.Asn288Stop. This mutation is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. This variant is found in OAPEO-MITOP panel(s).
Athena Diagnostics Inc	RCV000199034	SCV000615441	pathogenic	not provided	2017-06-30	criteria provided, single submitter	clinical testing
Invitae	RCV000194085	SCV001203355	pathogenic	Hereditary spastic paraplegia 7	2023-08-10	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. This sequence change creates a premature translational stop signal (Splice site) 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 (rs747863986, gnomAD 0.006%). This premature translational stop signal has been observed in individuals with autosomal recessive hereditary spastic paraplegia (PMID: 22964162, 23065789, 24727571). ClinVar contains an entry for this variant (Variation ID: 212294).
Paris Brain Institute, Inserm - ICM	RCV000194085	SCV001451039	pathogenic	Hereditary spastic paraplegia 7		criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV000194085	SCV002813260	pathogenic	Hereditary spastic paraplegia 7	2021-10-18	criteria provided, single submitter	clinical testing
Wellcome Centre for Mitochondrial Research, Newcastle University	RCV000508824	SCV000575907	pathogenic	Mitochondrial disease	2017-04-07	no assertion criteria provided	clinical testing