ClinVar Miner

Submissions for variant NM_003119.4(SPG7):c.1715C>T (p.Ala572Val) (rs72547551)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000413737 SCV000491195 likely pathogenic not provided 2016-09-28 criteria provided, single submitter clinical testing The A572V variant in the SPG7 gene has been reported previously in the compound heterozygous state in multiple individuals with spastic paraplegia and/or ataxia (Wilkinson et al., 2004; Klebe et al., 2012; Sanchez-Ferrero et al., 2013; Pfeffer et al., 2015; Choquet et al., 2015; Pyle et al., 2015). The A572V variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The A572V variant is a conservative amino acid substitution, which occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. The A572V variant is a strong candidate for a pathogenic variant, however the possibility it may be a rare benign variant cannot be excluded.
Invitae RCV000235251 SCV000640072 pathogenic Spastic paraplegia 7 2018-05-25 criteria provided, single submitter clinical testing This sequence change replaces alanine with valine at codon 572 of the SPG7 protein (p.Ala572Val). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and valine. This variant is present in population databases (rs72547551, ExAC 0.002%). This variant has been reported to segregate with autosomal recessive hereditary spastic paraplegia in several families (PMID: 25681447, 26626314). This variant has also been reported with a second pathogenic SPG7 allele in individuals affected with autosomal recessive hereditary spastic paraplegia (PMID: 14985266, 25681447, 26626314, 23065789). ClinVar contains an entry for this variant (Variation ID: 217269). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. For these reasons, this variant has been classified as Pathogenic.
Neurogenetics of motion laboratory,Montreal Neurological Institute RCV000235251 SCV000245721 pathogenic Spastic paraplegia 7 criteria provided, single submitter case-control

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