ClinVar Miner

Submissions for variant NM_003119.4(SPG7):c.2014G>A (p.Gly672Arg)

gnomAD frequency: 0.00004  dbSNP: rs369503365
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000640984 SCV000762594 pathogenic Hereditary spastic paraplegia 7 2022-11-01 criteria provided, single submitter clinical testing This missense change has been observed in individuals with hereditary spastic paraplegia (PMID: 18799786, 22964162, 29246610, 30747022). ClinVar contains an entry for this variant (Variation ID: 533739). This variant is present in population databases (rs369503365, gnomAD 0.008%). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt SPG7 protein function. For these reasons, this variant has been classified as Pathogenic. This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 672 of the SPG7 protein (p.Gly672Arg).
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV004526729 SCV005039706 pathogenic Hereditary pancreatitis 2024-03-19 criteria provided, single submitter clinical testing
PROSPAX: an integrated multimodal progression chart in spastic ataxias, Center for Neurology; Hertie-Institute for Clinical Brain Research RCV000640984 SCV005044558 likely pathogenic Hereditary spastic paraplegia 7 2022-01-01 criteria provided, single submitter research
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000640984 SCV005062059 pathogenic Hereditary spastic paraplegia 7 2024-03-19 criteria provided, single submitter clinical testing Variant summary: SPG7 c.2014G>A (p.Gly672Arg) results in a non-conservative amino acid change located in the Peptidase M41 domain (IPR000642) of the encoded protein sequence. Four of four in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 8e-06 in 250784 control chromosomes. c.2014G>A has been reported in the literature in at-least four individuals affected with Hereditary Spastic Paraplegia 7 and in each case, it was seen at a compound heterozygous state with different pathogenic variants (example, Almomen_2019, Benkirane_2021, van Gassen_2012). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 30747022, 34234304, 22964162). ClinVar contains an entry for this variant (Variation ID: 533739). Based on the evidence outlined above, the variant was classified as pathogenic.
Fulgent Genetics, Fulgent Genetics RCV000640984 SCV005642521 pathogenic Hereditary spastic paraplegia 7 2024-03-20 criteria provided, single submitter clinical testing

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