ClinVar Miner

Submissions for variant NM_003119.3(SPG7):c.1454_1462delGGCGGGAGA (p.Arg485_Glu487del) (rs768823392)

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Total submissions: 12
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000622361 SCV000741674 pathogenic Inborn genetic diseases 2016-07-18 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: POSITIVE: Relevant Alteration(s) Detected
Athena Diagnostics Inc RCV000479409 SCV000615432 pathogenic not provided 2015-07-14 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000479409 SCV000608793 likely pathogenic not provided 2018-02-28 criteria provided, single submitter clinical testing
Centre for Mendelian Genomics,University Medical Centre Ljubljana RCV000626835 SCV000747538 pathogenic Dysarthria; Gait ataxia; Cerebral cortical atrophy; Spastic paraparesis 2017-01-01 criteria provided, single submitter clinical testing
Centre for Mendelian Genomics,University Medical Centre Ljubljana RCV000626836 SCV000747539 pathogenic Seizures; Memory impairment; Gait ataxia; Spastic paraplegia 2017-01-01 criteria provided, single submitter clinical testing
GeneDx RCV000479409 SCV000566111 pathogenic not provided 2017-10-17 criteria provided, single submitter clinical testing The c.1454_1462delGGCGGGAGA (also reported as c.1450_1458del due to alternativenomenclature) in the SPG7 gene has been reported previously in association with spastic paraplegia. Most affectedindividuals were homozygous or compound heterozyogous for SPG7 variants and had typical features of spasticparaplegia 7 (McDermott et al., 2001; van Gassen et al., 2012; Klebe et al., 2012). When reported in theheterozygous state, some individuals had a later onset and milder presentation, sometimes with a cerebellar phenotypewithout spasticity (McDermott et al., 2001; Klebe et al., 2012). The c.1454_1462delGGCGGGAGA variant resultsin an in-frame deletion of three amino acid residues from the resulting protein starting with codon Arginine 485 andending with codon Glutamine 487, denoted p.Arg485_Glu487del. The c.1454_1462delGGCGGGAGA variant wasobserved in approximately 0.15% (12/8254 alleles) in individuals of European ancestry in the NHLBI ExomeSequencing Project. Therefore, we interpret c.1454_1462delGGCGGGAGA variant as a pathogenic variant.
Genetic Services Laboratory, University of Chicago RCV000475192 SCV000597235 likely pathogenic Spastic paraplegia 7 2016-12-23 criteria provided, single submitter clinical testing
Institute of Human Genetics,Cologne University RCV000664257 SCV000787826 uncertain significance Distal spinal muscular atrophy 2018-04-26 no assertion criteria provided clinical testing
Invitae RCV000475192 SCV000552958 pathogenic Spastic paraplegia 7 2018-01-31 criteria provided, single submitter clinical testing This variant, c.1454_1462delGGCGGGAGA, results in the deletion of 3 amino acids of the SPG7 protein (p.Arg485_Glu487del), but otherwise preserves the integrity of the reading frame. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has been reported in individuals affected with HSP from multiple (over 20) families. In many of these families, it has been reported to co-segregate with disease and, in affected individuals, has been observed on the opposite chromosome (in trans) from pathogenic variants (PMID: 11222789, 22964162, 23065789, 23269439, 23812641, 24466038, 24727571, 26756429, 27165006). ClinVar contains an entry for this variant (Variation ID: 411680). Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the deleted amino acids is currently unknown. In summary, this is a rare in-frame deletion that has been reported in trans with a pathogenic variant in affected individuals and has been reported to segregate with disease in many families. For these reasons, this variant has been classified as Pathogenic.
Mayo Clinic Genetic Testing Laboratories,Mayo Clinic RCV000475192 SCV000809094 pathogenic Spastic paraplegia 7 2018-06-13 criteria provided, single submitter clinical testing
Oxford Medical Genetics Laboratories,Oxford University Hospitals NHS Foundation Trust RCV000475192 SCV000926206 pathogenic Spastic paraplegia 7 2019-05-03 no assertion criteria provided clinical testing
Unit for Genetic & Epidemiological Research on Neurological Disorders,Instituto de Investigação e Inovação em Saúde RCV000516115 SCV000574448 pathogenic Hereditary spastic paraplegia 2017-03-07 criteria provided, single submitter research

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