Submissions for variant NM_000377.3(WAS):c.832G>T (p.Glu278Ter)

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Lifecell International Pvt. Ltd	RCV003159554	SCV003842268	likely pathogenic	X-linked severe congenital neutropenia		criteria provided, single submitter	clinical testing	A Homozygote Nonsense variant c.832G>T in Exon 9 of the WAS gene that results in the amino acid substitution p.Glu278* was identified. The observed variant has a minor allele frequency of 0.000% in gnomAD exomes and genomes, respectively. The severity of the impact of this variant on the protein is high, based on the effect of the protein and REVEL score. Rare Exome Variant Ensemble Learner (REVEL) is an ensembl method for predicting the pathogenicity of missense variants based on a combination of scores from 13 individual tools: MutPred, FATHMM v2.3, VEST 3.0, PolyPhen-2, SIFT, PROVEAN, MutationAssessor, MutationTaster, LRT, GERP++, SiPhy, phyloP, and phastCons. The REVEL score for an individual missense variant can range from 0 to 1, with higher scores reflecting greater likelihood that the variant is disease-causing. Mutations in this gene have been associated with Wiskott-Aldrich syndrome in multiple patients (Massaad, et al., 2013) Based on the above evidence this variant has been classified as Likely Pathogenic according to the ACMG guidelines.