Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
New York Genome Center | RCV002266645 | SCV002548683 | uncertain significance | Microcephaly 18, primary, autosomal dominant | 2021-07-16 | criteria provided, single submitter | clinical testing | The c.9260G>T (p.Cys3087Phe) variant identified in the WDFY3 gene substitutes a very well conserved Cysteine for Phenylalanine at amino acid 3087/3527 (exon 61/68). This variant is absent from gnomAD(v3.1.1) suggesting it is not a common benign variant in the populations represented in that database. In silico algorithms predict this variant to be Damaging (SIFT; score:0.001) and Benign (REVEL; score:0.4519) to the function of the canonical transcript. This variant is absent from ClinVar and to our current knowledge has not been reported in affected individuals in the literature. The p.Cys3087 residue is within the first WD domain of WDFY3 (UniProtKB:Q8IZQ1). Given the lack of compelling evidence for its pathogenicity, the c.9260G>T (p.Cys3087Phe) variant identified in the WDFY3 gene is reported as a Variant of Uncertain Significance. |