Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Genomic Diagnostic Laboratory, |
RCV000239291 | SCV000297212 | pathogenic | not provided | 2015-11-08 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001854921 | SCV002109329 | pathogenic | Hereditary spastic paraplegia 47 | 2023-11-06 | criteria provided, single submitter | clinical testing | This sequence change affects an acceptor splice site in intron 2 of the AP4B1 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 AP4B1 are known to be pathogenic (PMID: 22290197, 24700674, 24781758). This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individuals with hereditary spastic paraplegia (PMID: 29193663). ClinVar contains an entry for this variant (Variation ID: 252667). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |
Genome- |
RCV001854921 | SCV004050708 | pathogenic | Hereditary spastic paraplegia 47 | 2023-04-11 | criteria provided, single submitter | clinical testing | |
Yale Center for Mendelian Genomics, |
RCV001849350 | SCV002106829 | likely pathogenic | Spastic paraplegia | 2020-10-01 | no assertion criteria provided | literature only |