Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| New York Genome Center | RCV001420545 | SCV001622850 | uncertain significance | Intellectual disability, autosomal recessive 43 | 2020-06-19 | criteria provided, single submitter | clinical testing | The inherited c.2423G>A (p.Arg808Gln) variant identified in the WASHC4 gene substitutes a well conserved Arginine for Glutamine at amino acid 808/1174 (coding exon 24/33). This variant is found with low frequency in gnomAD (v3.0) (12 heterozygotes, 0 homozygotes; allele frequency: 8.38e-5) suggesting it is not a common benign variant in the populations represented in that database. In silico algorithms predict this variant to be Neutral (Provean; score: -1.63) and Tolerated (SIFT; score:0.147) 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.Arg808 residue is not within a mapped domain of WASHC4, but is within a region of the protein sufficient for interaction with WASHC5 (UniProtKB: Q2M389). Given the lack of compelling evidence for its pathogenicity, the inherited c.2423G>A (p.Arg808Gln) variant identified in the WASHC4 gene is reported here as a Variant of UncertainSignificance. |
| Ambry Genetics | RCV004038180 | SCV004979456 | uncertain significance | not specified | 2022-07-20 | criteria provided, single submitter | clinical testing | The c.2423G>A (p.R808Q) alteration is located in exon 24 (coding exon 24) of the KIAA1033 gene. This alteration results from a G to A substitution at nucleotide position 2423, causing the arginine (R) at amino acid position 808 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |