Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Neurometabolic Diseases Laboratory, |
RCV001785414 | SCV003920789 | pathogenic | Spastic paraplegia 84, autosomal recessive | 2023-04-27 | criteria provided, single submitter | research | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV003479351 | SCV004223132 | uncertain significance | not specified | 2023-11-22 | criteria provided, single submitter | clinical testing | Variant summary: PI4KA c.4666G>A (p.Val1556Met) results in a conservative amino acid change located in the phosphoinositide 3-kinase, accessory (PIK) domain (IPR001263) of the encoded protein sequence. Two of four in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00018 in 248792 control chromosomes (gnomAD). c.4666G>A has been reported in the literature in the compound heterozygous state in an individual affected with spastic paraplegia and mild intellectual disability (Verdura_2021). This report does not provide unequivocal conclusions about association of the variant with PI4KA-Related Disorders. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication has been ascertained in the context of this evaluation (PMID: 34415322). No clinical diagnostic laboratories have cited clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance. |
Gene |
RCV004591566 | SCV005079780 | uncertain significance | not provided | 2023-11-22 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 34415322) |
OMIM | RCV001785414 | SCV002026469 | pathogenic | Spastic paraplegia 84, autosomal recessive | 2022-09-28 | no assertion criteria provided | literature only |