Submissions for variant NM_001386393.1(PANK2):c.1083-3_1083-2del

dbSNP: rs760705943

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV001479527	SCV001683826	likely benign	Pigmentary pallidal degeneration	2023-10-28	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV002271601	SCV002556168	uncertain significance	not specified	2022-06-24	criteria provided, single submitter	clinical testing	Variant summary: PANK2 c.1413-3_1413-2delCA deletes 2 nucleotides at a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 4/4 computational tools predict no significant impact on normal splicing as an upstream nucleotide preserves the splice site, however, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00012 in 246082 control chromosomes (gnomAD). This frequency is not significantly higher than expected for a pathogenic variant in PANK2 causing Pantothenate Kinase-Associated Neurodegeneration (0.00012 vs 0.0011), allowing no conclusion about variant significance. To our knowledge, no occurrence of c.1413-3_1413-2delCA in individuals affected with Pantothenate Kinase-Associated Neurodegeneration and no experimental evidence demonstrating its impact on protein function have been reported. One ClinVar submitter has assessed the variant since 2014: the variant was classified as likely benign. Based on the evidence outlined above, the variant was classified as uncertain significance.
PreventionGenetics, part of Exact Sciences	RCV003970758	SCV004782992	likely benign	PANK2-related disorder	2019-09-19	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).