Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| New York Genome Center | RCV001542346 | SCV001761034 | uncertain significance | Microcephaly 18, primary, autosomal dominant | 2020-07-14 | criteria provided, single submitter | clinical testing | The de novo c.5404C>T (p.Arg1802Trp) variant identified in the WDFY3 gene of this individual substitutes a conserved Arginine for Tryptophan at amino acid 1802/3527 (exon 33/68). This variant is found with low frequency in gnomAD(v2.1.1) (4 heterozygotes, 0 homozygotes; allele frequency: 1.59e-5) suggesting it is not a common benign variant in the populations represented in that database, however these 4 heterozygous individuals are reported in the non-neuro cohort of gnomAD(v2.1.1) (rs138292353). In silico algorithms do not agree on the effect of this variant, as it is predicted both Neutral (Provean; score: -0.3) and Damaging (SIFT; score: 0.009) 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.Arg1802 residue is not within a mapped domain of WDFY3. While the c.5404C>T (p.Arg1802Trp) variant is identified de novo in this individual, its presence in 4 individuals within the non-Neuro cohort of gnomAD(v2.1.1) and the absence of additional evidence supporting its pathogenicity results in its classification as a Variant of Uncertain Significance |
| Gene |
RCV003442890 | SCV004169173 | uncertain significance | not provided | 2023-04-18 | criteria provided, single submitter | clinical testing | Observed in an individual from a large cohort of patients with autism (Guo et al., 2018); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 30564305) |