ClinVar Miner

Submissions for variant NM_003119.4(SPG7):c.233T>A (p.Leu78Ter)

gnomAD frequency: 0.00014  dbSNP: rs121918358
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Total submissions: 17
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Neurogenetics of motion laboratory, Montreal Neurological Institute RCV000007218 SCV000245724 pathogenic Hereditary spastic paraplegia 7 criteria provided, single submitter case-control
GeneDx RCV000200640 SCV000252327 pathogenic not provided 2022-02-07 criteria provided, single submitter clinical testing Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 25525159, 27084228, 28362824, 29482223, 18200586, 23065789, 22571692, 26626314, 22964162, 25681447, 25976027, 31433872, 31407473, 33300680, 31589614, 33084218, 33624863)
Invitae RCV000007218 SCV000640076 pathogenic Hereditary spastic paraplegia 7 2023-11-09 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Leu78*) 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 (rs121918358, gnomAD 0.3%), including at least one homozygous and/or hemizygous individual. This premature translational stop signal has been observed in individual(s) with clinical features of autosomal recessive hereditary spastic paraplegia (PMID: 18200586, 22571692, 24727571). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 6816). For these reasons, this variant has been classified as Pathogenic.
Athena Diagnostics RCV000200640 SCV000844104 pathogenic not provided 2017-12-22 criteria provided, single submitter clinical testing
Genomic Research Center, Shahid Beheshti University of Medical Sciences RCV000007218 SCV000930176 pathogenic Hereditary spastic paraplegia 7 2020-05-03 criteria provided, single submitter clinical testing
Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München RCV000007218 SCV001149940 pathogenic Hereditary spastic paraplegia 7 2019-06-07 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV000200640 SCV001246155 pathogenic not provided 2023-07-01 criteria provided, single submitter clinical testing SPG7: PM3:Very Strong, PVS1, PM2
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen RCV000200640 SCV001447026 pathogenic not provided 2020-10-23 criteria provided, single submitter clinical testing
Paris Brain Institute, Inserm - ICM RCV000007218 SCV001451030 pathogenic Hereditary spastic paraplegia 7 criteria provided, single submitter clinical testing
Baylor Genetics RCV000007218 SCV001522926 pathogenic Hereditary spastic paraplegia 7 2020-01-16 criteria provided, single submitter clinical testing This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868].
Institute of Human Genetics, University of Leipzig Medical Center RCV000007218 SCV001934454 pathogenic Hereditary spastic paraplegia 7 2021-02-24 criteria provided, single submitter clinical testing This variant was identified as compound heterozygous with NM_003119.4:c.1529C>T.
Genome Diagnostics Laboratory, The Hospital for Sick Children RCV001847594 SCV002105885 pathogenic Hereditary spastic paraplegia 2021-03-01 criteria provided, single submitter clinical testing
MGZ Medical Genetics Center RCV000007218 SCV002580802 pathogenic Hereditary spastic paraplegia 7 2023-02-20 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV000007218 SCV002809350 likely pathogenic Hereditary spastic paraplegia 7 2021-12-20 criteria provided, single submitter clinical testing
Neuberg Centre For Genomic Medicine, NCGM RCV000007218 SCV004047753 pathogenic Hereditary spastic paraplegia 7 criteria provided, single submitter clinical testing The stop gained variant c.233T>A (p.Leu78Ter) in SPG7 gene has been observed in the literature in the homozygous state in 5 individuals from 3 families affected with HSP (Sanchez-Ferrero E et.al.,2013). This variant has been reported to the ClinVar database as Pathogenic. The c.233T>A variant is reported with allele frequency 0.04% in gnomAD exomes and novel in 1000 Genomes. The nucleotide change c.233T>A in SPG7 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. This variant is predicted to cause loss of normal protein function. Loss of function variants have been previously reported to be disease causing. For these reasons, this variant has been classified as Pathogenic. Variant s in SPG7 genes are known to have both Autosomal dominant and Autosomal recessive pat t ern of inheritance (OMIM #607259)[1,2]. However, Autosomal dominant inheritance is not report ed for this variant in lit erature yet .
OMIM RCV000007218 SCV000027414 pathogenic Hereditary spastic paraplegia 7 2008-04-01 no assertion criteria provided literature only
Institute of Human Genetics, Cologne University RCV000664258 SCV000787827 uncertain significance Proximal spinal muscular atrophy 2018-04-26 no assertion criteria provided clinical testing

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