Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000780795 | SCV000918356 | likely pathogenic | Wiskott-Aldrich syndrome | 2017-09-13 | criteria provided, single submitter | clinical testing | Variant summary: The WAS c.257G>C (p.Arg86Pro) variant involves the alteration of a conserved nucleotide, resulting in a missense change that lies within the WH1/EVH1 domain (InterPro). 4/4 in silico tools predict a damaging outcome for this variant. This variant is absent in 72521 control chromosomes (ExAC). The variant has been reported in at least one Wiskott-Aldrich syndrome patient with a severe phenotype (Schindelhauer_1996). In addition, codon 86 is a mutational hotspot where 5 overlapping variants have been reported in patients (R86H, R86C, R86G, R86L, and R86S); all reported as "pathogenic" in ClinVar. Additionally, a functional study showed that the overlapping R86H variant impairs the interaction between WAS protein and an interacting protein, WIP (Stewart_1999). Taken together, by applying ACMG rules, this variant is classified as Likely Pathogenic, until additional information specific to the R86P variant are available. |