Submissions for variant NM_003119.4(SPG7):c.1552+1G>T

gnomAD frequency: 0.00003  dbSNP: rs141644720

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München	RCV000995648	SCV001149942	pathogenic	Hereditary spastic paraplegia 7	2019-06-07	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001091056	SCV001246895	pathogenic	not provided	2022-05-01	criteria provided, single submitter	clinical testing	SPG7: PVS1, PM3:Strong, PM2
Labcorp Genetics (formerly Invitae), Labcorp	RCV000995648	SCV001390280	pathogenic	Hereditary spastic paraplegia 7	2022-05-16	criteria provided, single submitter	clinical testing	Disruption of this splice site has been observed in individuals with spastic paraplegia (PMID: 20108356, 31407473). ClinVar contains an entry for this variant (Variation ID: 807498). Studies have shown that disruption of this splice site results in mRNA lacking exon 11 and introduces a premature termination codon (PMID: 20108356). The resulting mRNA is expected to undergo nonsense-mediated decay. For these reasons, this variant has been classified as Pathogenic. This variant is present in population databases (rs141644720, gnomAD 0.004%). This sequence change affects a donor splice site in intron 11 of the SPG7 gene. RNA analysis indicates that disruption of this splice site induces altered splicing and may result in an absent or disrupted protein product.
Paris Brain Institute, Inserm - ICM	RCV000995648	SCV001451055	pathogenic	Hereditary spastic paraplegia 7		criteria provided, single submitter	clinical testing
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	RCV001091056	SCV001905572	pathogenic	not provided	2021-09-15	criteria provided, single submitter	clinical testing
Institute of Human Genetics, University of Leipzig Medical Center	RCV000995648	SCV001949993	pathogenic	Hereditary spastic paraplegia 7	2021-04-08	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	RCV001847130	SCV002105847	likely pathogenic	Hereditary spastic paraplegia	2018-09-01	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV000995648	SCV002785427	pathogenic	Hereditary spastic paraplegia 7	2021-07-12	criteria provided, single submitter	clinical testing
PROSPAX: an integrated multimodal progression chart in spastic ataxias, Center for Neurology; Hertie-Institute for Clinical Brain Research	RCV000995648	SCV005044581	pathogenic	Hereditary spastic paraplegia 7	2022-01-01	criteria provided, single submitter	research
Zotz-Klimas Genetics Lab, MVZ Zotz Klimas	RCV000995648	SCV004101096	pathogenic	Hereditary spastic paraplegia 7	2023-11-02	no assertion criteria provided	clinical testing