Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000549719 | SCV000640191 | uncertain significance | Kufor-Rakeb syndrome; Autosomal recessive spastic paraplegia type 78 | 2023-03-05 | criteria provided, single submitter | clinical testing | 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 is not likely to affect RNA splicing. ClinVar contains an entry for this variant (Variation ID: 465260). This variant has not been reported in the literature in individuals affected with ATP13A2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change affects codon 804 of the ATP13A2 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the ATP13A2 protein. This variant also falls at the last nucleotide of exon 21, which is part of the consensus splice site for this exon. |
| Ambry Genetics | RCV002448695 | SCV002732814 | uncertain significance | Inborn genetic diseases | 2019-08-22 | criteria provided, single submitter | clinical testing | The c.2412G>A variant (also known as p.K804K), located in coding exon 21 of the ATP13A2 gene, results from a G to A substitution at nucleotide position 2412. This nucleotide substitution does not change the at codon 804. However, this change occurs in the last base pair of coding exon 21, which makes it likely to have some effect on normal mRNA splicing. This nucleotide position is highly conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is predicted to weaken the efficiency of the native splice donor site; however, direct evidence is unavailable. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |