Table 1 Functional annotation of the thirteen EPHB4 variants investigated in this study.

From: Janus-faced EPHB4-associated disorders: novel pathogenic variants and unreported intrafamilial overlapping phenotypes

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  1. Genomic coordinates, nucleotide and protein changes, predicted pathogenicity, and population allele frequencies are summarized. All previously reported EPHB4 variants for the GLDUK, GLDNOR, and CM-AVM2 cases and EPHB4 variants of uncertain significance (VUS) for the FH1–FH5, VA1–VA2, and PL1 cases are either not reported in gnomAD databases or their allele frequency is infinitesimal, supporting the argument that they are extremely rare in the general population, while they are all reported to be pathogenic by all three prediction tools used (CADD, PolyPhen-2, MutationTaster). The three EPHB4 variants used as controls (SNP) in this study are reported as rare variants (AF < 0.01) in gnomAD databases. Two of them are found in homozygotes and/or are predicted as pathogenic. GLDUK and GLDNOR published in Martin-Almedina et al.2 and CM-AVM2 in Yu et al.5
  2. AF allele frequency, CM-AVM capillary malformation–arteriovenous malformation, FH fetal hydrops, FND fibronectin domain, LBD ligand binding domain, PL primary lymphedema, SNP single-nucleotide polymorphism (likely benign variant), TKD tyrosine kinase domain, VA vascular anomalies.
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