Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Neuberg Centre For Genomic Medicine, |
RCV004771643 | SCV005382282 | uncertain significance | Developmental delay, impaired speech, and behavioral abnormalities, with or without seizures | 2023-05-20 | criteria provided, single submitter | clinical testing | The observed missense variant c.784G>A(p.Glu262Lys in ARFGEF1 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The c.784G>A variant has 0.002% allele frequency in gnomAD Exomes. The amino acid Glutamic acid at position 262 is changed to a Lysine changing protein sequence and it might alter its composition and physico-chemical properties. The reference amino acid in ARFGEF1 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. Computational evidence (Polyphen, SIFT and Mutation Taster) predicts conflicting evidence on protein structure and function for this variant. For these reasons, this variant has been classified as Uncertain Significance. |