ClinVar

Description

Variant summary: The variant involves the deletion of exons 30-31 and a part of exon 32 (i.e. the last exon) in the PHKA1 gene. As it encompasses the last exons, it is predicted to escape nonsense mediated decay (NMD). A presumed nomenclature of c.(3243+1_3244-1)_3598del has been designated for the purposes of this classification. This variant is expected to result in a large deletion change in the PHKA1 gene, removing part of the C-terminal domain (IPR045583) of the encoded protein. The variant was absent in 16120 control chromosomes in the gnomAD database (Structural Variants v2.1 dataset). To our knowledge, no occurrence of c.(3243+1_3244-1)_3598del in individuals affected with Glycogen Phosphorylase Kinase Deficiency and no experimental evidence demonstrating its impact on protein function have been reported. However, multiple variants have been reported in the deleted region in affected individuals (HGMD), which might indicate a functional importance for the deleted protein region. No submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic.