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 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. 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 variant has been observed in individuals with hereditary spastic paraplegia (PMID: 23733235). This variant is present in population databases (rs765178985, gnomAD 0.007%). 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.
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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