ClinVar Miner

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

dbSNP: rs797046003
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Total submissions: 9
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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 RCV000199034 SCV000615441 pathogenic not provided 2017-06-30 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000194085 SCV001203355 pathogenic Hereditary spastic paraplegia 7 2024-12-09 criteria provided, single submitter clinical testing 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). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
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
PROSPAX: an integrated multimodal progression chart in spastic ataxias, Center for Neurology; Hertie-Institute for Clinical Brain Research RCV000194085 SCV005044589 pathogenic Hereditary spastic paraplegia 7 2022-01-01 criteria provided, single submitter research
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000194085 SCV005727081 pathogenic Hereditary spastic paraplegia 7 2024-11-05 criteria provided, single submitter clinical testing Variant summary: SPG7 c.861dupT (p.Asn288X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Consensus agreement among computation tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 2.8e-05 in 249950 control chromosomes. To our knowledge, no occurrence of c.861dupT in individuals affected with Hereditary Spastic Paraplegia 7 and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 212294). Based on the evidence outlined above, the variant was classified as pathogenic.
Wellcome Centre for Mitochondrial Research, Newcastle University RCV000508824 SCV000575907 pathogenic Mitochondrial disease 2017-04-07 no assertion criteria provided clinical testing

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