ClinVar Miner

Submissions for variant NM_003119.4(SPG7):c.637C>T (p.Arg213Ter) (rs774774648)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000725648 SCV000338358 pathogenic not provided 2015-12-14 criteria provided, single submitter clinical testing
Invitae RCV000276883 SCV000762587 pathogenic Spastic paraplegia 7 2017-10-24 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg213*) in the SPG7 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs774774648, ExAC 0.05%). This variant has been reported as heterozygous in an individual affected with sporadic amyotrophic lateral sclerosis. A second variant in SPG7 was not reported in this individual (PMID: 27790088). ClinVar contains an entry for this variant (Variation ID: 285368). Loss-of-function variants in SPG7 are known to be pathogenic (PMID: 14722615, 16357941). For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV000725648 SCV000890847 pathogenic not provided 2019-01-22 criteria provided, single submitter clinical testing The R213X pathogenic variant in the SPG7 gene was initially reported in an individual with sporadic amyotrophic lateral sclerosis (Kruger et al., 2016). This variant was subsequently observed in an individual with ataxia who harbored a second pathogenic SPG7 variant (Mancini et al., 2018). The R213X variant is observed in 7/17,248 (0.04%) alleles from individuals of East Asian background (Lek et al., 2016). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay.
Illumina Clinical Services Laboratory,Illumina RCV000276883 SCV000914743 uncertain significance Spastic paraplegia 7 2019-01-11 criteria provided, single submitter clinical testing The SPG7 c.637C>T (p.Arg213Ter) variant has been reported in one study and is found in one patient with hereditary spastic paraplegia in a compound heterozygous state (Mancini et al. 2019). Control data are unavailable for this variant, which is reported at a frequency of 0.000462 in the East Asian population of the Exome Aggregation Consortium. Based on the limited clinical evidence and the potential impact of stop-gained variants, the p.Arg213Ter variant is classified as a variant of unknown significance but suspicious for pathogenicity for autosomal recessive hereditary spastic paraplegia. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
GenomeConnect, ClinGen RCV000276883 SCV000784708 not provided Spastic paraplegia 7 no assertion provided phenotyping only GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.

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