Compound heterozygous WNT10A missense variations exacerbated the tooth agenesis caused by hypohidrotic ectodermal dysplasia

Table 2 The pathogenicity of three variations were predicted by in silico tools

Variation	dbSNPs	SIFT	PolyPhen-2	CADD	ACMG
EDA c.878 T > G (p.L293R)	Unknown	D (0)	D (0.995)	29.1	Uncertain significance PM1 + PM2
WNT10A c.511C > T (p.R171C)	rs116998555	D (0)	D (0.93)	32	Uncertain significance PP5 + BS1
WNT10A c.637G > A (p.G213S)	rs147680216	D (0.001)	D (0.999)	33	Uncertain significance PP1 + PP3

SIFT D Deleterious (≤0.05), T Tolerated (> 0.05), PolyPhen-2 D Probably damaging (≥0.909), P Possibly damaging (0.447 ≤ polyphen-2 ≤ 0.909), B Benign (≤0.446). CADD > 20 considered harmful for variation. ACMG PM1: Located in a mutational hot spot and/or critical and well-established functional domain without benign variation; PM2 Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation; PP1 Cosegregation with disease in multiple affected family members in a gene definitively known to cause the disease; PP3 Multiple lines of computational evidence support a deleterious effect on the gene or gene product; PP5 Reputable source recently reports variant as pathogenic, but the evidence is not available to the laboratory to perform an independent evaluation; BS1 Allele frequency is greater than expected for disorder

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