Submissions for variant NM_022089.4(ATP13A2):c.2251+5A>G

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003002397	SCV003295461	uncertain significance	Kufor-Rakeb syndrome; Autosomal recessive spastic paraplegia type 78	2022-08-31	criteria provided, single submitter	clinical testing	This sequence change falls in intron 20 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 (rs763122225, gnomAD 0.009%). This variant has not been reported in the literature in individuals affected with ATP13A2-related conditions. 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.
Ambry Genetics	RCV003002396	SCV003548607	uncertain significance	Inborn genetic diseases	2021-11-25	criteria provided, single submitter	clinical testing	The c.2251+5A>G intronic alteration consists of a A to G substitution 5 nucleotides after exon 20 of the ATP13A2 gene. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.