ClinVar

Description

Variant summary: KYNU c.291-7A>G alters a conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. Several computational tools predict a significant impact on normal splicing: Four predict the variant creates a cryptic 3' acceptor site. Two predict the variant weakens a 3' acceptor site. Two predict the variant abolishes a 3' acceptor site. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 9.6e-05 in 251268 control chromosomes (gnomAD). To our knowledge, no occurrence of c.291-7A>G in individuals affected with Vertebral, Cardiac, Renal, And Limb Defects Syndrome 2 and no experimental evidence demonstrating its impact on protein function have been reported. One submitter has cited clinical-significance assessments for this variant to ClinVar after 2014 and has classified the variant as likely benign. Based on the evidence outlined above, the variant was classified as uncertain significance.