Submissions for variant NM_003119.4(SPG7):c.861+1G>C

gnomAD frequency: 0.00001  dbSNP: rs1412575396

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Molecular Diagnostics Laboratory, M Health Fairview: University of Minnesota	RCV000761358	SCV000891344	likely pathogenic	Hereditary spastic paraplegia 7	2017-06-22	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000761358	SCV003027959	pathogenic	Hereditary spastic paraplegia 7	2022-02-19	criteria provided, single submitter	clinical testing	This variant is present in population databases (no rsID available, gnomAD 0.002%). For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 623233). Disruption of this splice site has been observed in individuals with hereditary spastic paraplegia (PMID: 31433872; Invitae). This sequence change affects a donor splice site in intron 6 of the SPG7 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in SPG7 are known to be pathogenic (PMID: 21623769, 22964162).
PROSPAX: an integrated multimodal progression chart in spastic ataxias, Center for Neurology; Hertie-Institute for Clinical Brain Research	RCV000761358	SCV005044520	pathogenic	Hereditary spastic paraplegia 7	2022-01-01	criteria provided, single submitter	research
Mayo Clinic Laboratories, Mayo Clinic	RCV004792432	SCV005413158	pathogenic	not provided	2024-07-10	criteria provided, single submitter	clinical testing	PM2, PS1_supporting, PVS1