Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Laboratory Services, |
RCV000778581 | SCV000914885 | uncertain significance | WDR35-related disorder | 2018-11-06 | criteria provided, single submitter | clinical testing | This variant is a stop-gained variant, which was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018) and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score for this variant, it could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change. No publications were found based on this search. Due to the potential impact of stop-gained variants and the lack of clarifying evidence, this variant is classified as a variant of unknown significance but suspicious for pathogenicity for this disease. |
| Neuberg Centre For Genomic Medicine, |
RCV004821291 | SCV005442675 | uncertain significance | Cranioectodermal dysplasia 2 | criteria provided, single submitter | clinical testing | The observed stop gained c.2842A>Tp.Lys948Ter variant in WDR35 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This variant is reported with the allele frequency of 0.005% in the gnomAD Exomes. This variant has been reported to the ClinVar database as Uncertain Significance. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. Loss of function variants have been previously reported to be disease causing. Computational evidence MutationTaster - Disease causing automatic predicts damaging effect on protein structure and function for this variant. However, study of the variant in multiple affected individuals and its functional impact on the protein is required to determine the pathogenicity of the variant. For these reasons, this variant has been classified as Uncertain Significance. | |
| Fulgent Genetics, |
RCV005029428 | SCV005654891 | likely pathogenic | Cranioectodermal dysplasia 2; Short-rib thoracic dysplasia 7 with or without polydactyly | 2023-12-29 | criteria provided, single submitter | clinical testing |