Submissions for variant NM_022089.4(ATP13A2):c.1039+6C>T

gnomAD frequency: 0.00035  dbSNP: rs565724504

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	RCV000767898	SCV000898537	uncertain significance	Kufor-Rakeb syndrome; Autosomal recessive spastic paraplegia type 78	2021-03-30	criteria provided, single submitter	clinical testing	ATP13A2 NM_022089 exon11 c.1039+6C>T: This variant has not been reported in the literature but is present in 10/32884 Latino alleles in the Genome Aggregation Database (http://gnomad.broadinstitute.org/rs565724504). Evolutionary conservation and computational predictive tools for this variant are limited or unavailable. This variant is an intronic variant with no predicted change in the amino acid sequence but may have an unknown effect on splicing. Further studies are needed to understand its impact. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
Invitae	RCV000767898	SCV001233567	uncertain significance	Kufor-Rakeb syndrome; Autosomal recessive spastic paraplegia type 78	2022-10-24	criteria provided, single submitter	clinical testing	This sequence change falls in intron 11 of the ATP13A2 gene. It does not directly change the encoded amino acid sequence of the ATP13A2 protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs565724504, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with ATP13A2-related conditions. ClinVar contains an entry for this variant (Variation ID: 625890). 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. 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.
CeGaT Center for Human Genetics Tuebingen	RCV002061035	SCV002496461	likely benign	not provided	2023-06-01	criteria provided, single submitter	clinical testing	ATP13A2: BP4, BS1
Fulgent Genetics, Fulgent Genetics	RCV000767898	SCV002805605	uncertain significance	Kufor-Rakeb syndrome; Autosomal recessive spastic paraplegia type 78	2021-10-06	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003975311	SCV004792059	likely benign	ATP13A2-related condition	2019-02-22	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).