Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Baylor Genetics | RCV000191064 | SCV000245454 | pathogenic | Kufor-Rakeb syndrome | 2013-01-29 | criteria provided, single submitter | clinical testing | This variant includes the the splice acceptor site of intron 4 and the first four nucleotides of exon 5. Because the splice acceptor site is deleted, it is categorized as deleterious according to ACMG guidelines (PMID:18414213). Found with another missense variant (G315R; phase undetermined) in a 54-year-old male with seizures, apraxia, progressive cognitive problems, confusion, speech difficulty, history of stroke. |
Eurofins Ntd Llc |
RCV000598141 | SCV000708759 | uncertain significance | not provided | 2017-05-30 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001378978 | SCV001576689 | likely pathogenic | Kufor-Rakeb syndrome; Autosomal recessive spastic paraplegia type 78 | 2023-01-03 | criteria provided, single submitter | clinical testing | In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely 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: 209135). This variant has not been reported in the literature in individuals affected with ATP13A2-related conditions. This variant is present in population databases (rs749798211, gnomAD 0.004%). This variant results in the deletion of part of exon 5 (c.348-9_351del) of the ATP13A2 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 ATP13A2 are known to be pathogenic (PMID: 16964263, 21696388). |