ClinVar Miner

Submissions for variant NM_014946.4(SPAST):c.1728+1G>A

dbSNP: rs587777754
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000686758 SCV000814291 pathogenic Hereditary spastic paraplegia 4 2022-08-20 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. 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. ClinVar contains an entry for this variant (Variation ID: 566838). This variant is also known as c.1853+1G>A. Disruption of this splice site has been observed in individuals with autosomal dominant herditary spastic paraplegia (PMID: 10699187, 15841487). This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 16 of the SPAST gene. While this variant is not anticipated to result in nonsense mediated decay, it likely alters RNA splicing and results in a disrupted protein product.
Paris Brain Institute, Inserm - ICM RCV000686758 SCV001451015 pathogenic Hereditary spastic paraplegia 4 criteria provided, single submitter clinical testing
GeneDx RCV003332228 SCV004039620 pathogenic not provided 2023-09-26 criteria provided, single submitter clinical testing Canonical splice site variant predicted to result in a null allele in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 31227335, 25525159, 29980238, 21546041, 31751864, 10699187, 15841487, 36825575, 30564185)
Athena Diagnostics RCV003332228 SCV005620743 pathogenic not provided 2024-10-18 criteria provided, single submitter clinical testing This variant is not expected to cause loss of protein expression through nonsense-mediated decay. However, similar variants in this region have been associated with disease, and therefore, this variant is also expected to associate with disease. This variant has been identified in multiple unrelated individuals with clinical features associated with this gene. In some published literature, this variant is referred to as c.1853+1G>A.

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