ClinVar Miner

Submissions for variant NM_003119.4(SPG7):c.861+6T>C

dbSNP: rs765178985
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001039955 SCV001203507 uncertain significance Hereditary spastic paraplegia 7 2022-02-04 criteria provided, single submitter clinical testing Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This sequence change falls in intron 6 of the SPG7 gene. It does not directly change the encoded amino acid sequence of the SPG7 protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs765178985, gnomAD 0.007%). This variant has been observed in individuals with hereditary spastic paraplegia (PMID: 23733235). ClinVar contains an entry for this variant (Variation ID: 838411). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Concord Molecular Medicine Laboratory, Concord Repatriation General Hospital RCV001039955 SCV005043118 pathogenic Hereditary spastic paraplegia 7 2024-05-08 criteria provided, single submitter clinical testing This variant was detected in trans to another pathogenic variant in SPG7 in a patient with progressive lower limb weakness and ataxia. This is a rare variant detected at a very low frequency in control population (allelic frequency 0.0003%, gnomAD v4.1). RNA studies from peripheral blood sample confirmed near complete loss of canonical exon 6-7 splicing, resulting in exon 6 skipping and cryptic donor site activation leading to a premature stop codon.

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