Submissions for variant NM_022089.4(ATP13A2):c.2836A>T (p.Ile946Phe)

gnomAD frequency: 0.00091  dbSNP: rs55708915

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genetic Services Laboratory, University of Chicago	RCV000116438	SCV000150363	uncertain significance	not provided	2014-02-07	criteria provided, single submitter	clinical testing
Invitae	RCV000550501	SCV000640194	likely benign	Kufor-Rakeb syndrome; Autosomal recessive spastic paraplegia type 78	2024-01-31	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002313855	SCV000848291	benign	Inborn genetic diseases	2021-02-03	criteria provided, single submitter	clinical testing	This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Genomic Research Center, Shahid Beheshti University of Medical Sciences	RCV000785011	SCV000923563	uncertain significance	Autosomal recessive spastic paraplegia type 78	2019-01-01	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001097255	SCV001253516	uncertain significance	Kufor-Rakeb syndrome	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Mayo Clinic Laboratories, Mayo Clinic	RCV000116438	SCV001715510	uncertain significance	not provided	2023-01-09	criteria provided, single submitter	clinical testing
GeneDx	RCV000116438	SCV001759516	likely benign	not provided	2021-01-08	criteria provided, single submitter	clinical testing	Reported in the heterozygous state in an individual with Parkinson disease; however, a second ATP13A2 variant was not detected and I946F was observed in an unaffected control (Djarmati et al., 2009); This variant is associated with the following publications: (PMID: 19458722, 18075584, 12169656, 19705361, 19085912, 18075585)
CeGaT Center for Human Genetics Tuebingen	RCV000116438	SCV004701251	uncertain significance	not provided	2024-01-01	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004549579	SCV004741260	likely benign	ATP13A2-related disorder	2022-12-01	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).
GenomeConnect - Invitae Patient Insights Network	RCV003483485	SCV004228802	not provided	Kufor-Rakeb syndrome; Autosomal recessive spastic paraplegia type 78; Parkinsonism due to ATP13A2 deficiency		no assertion provided	phenotyping only	Variant interpreted as Uncertain significance and reported on 12-28-2020 by Lab Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information.