Total submissions: 11
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Illumina Laboratory Services, |
RCV000288028 | SCV000426023 | likely pathogenic | WDR35-related disorder | 2017-04-27 | criteria provided, single submitter | clinical testing | The WDR35 c.1922T>G (p.Leu641Ter) variant is a stop-gained variant that has been reported in two studies in which it was found in two individuals with cranioectodermal dysplasia, both in a compound heterozygous state with a missense variant (Hoffer et al. 2013; Li et al. 2015). The variant was absent from 300 control chromosomes but is reported at a frequency of 0.00039 in the European (non-Finnish) population of the Exome Aggregation Consortium. Due to the potential impact of stop-gained variants and the supporting evidence, the p.Leu641Ter variant is classified as likely pathogenic for WDR35-related disorders. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. |
Labcorp Genetics |
RCV000648351 | SCV000770167 | pathogenic | Cranioectodermal dysplasia 2; Short-rib thoracic dysplasia 7 with or without polydactyly | 2023-12-12 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Leu641*) in the WDR35 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in WDR35 are known to be pathogenic (PMID: 22486404, 29068549). This variant is present in population databases (rs199952377, gnomAD 0.03%). This premature translational stop signal has been observed in individuals with cranioectodermal dysplasia, also known as Sensenbrenner syndrome (PMID: 22486404, 25914204, 28332779). ClinVar contains an entry for this variant (Variation ID: 65619). For these reasons, this variant has been classified as Pathogenic. |
Laboratory for Molecular Medicine, |
RCV000826131 | SCV000967645 | likely pathogenic | Cranioectodermal dysplasia | 2018-03-12 | criteria provided, single submitter | clinical testing | The p.Leu641X variant in WDR35 has been reported in 3 compound heterozygous indi viduals with cranioectodermal dysplasia (Hoffer 2013, Li 2015, Walczak-Sztulpa 2 017) and has been reported in ClinVar (Variation ID #65619). This variant has al so been identified in 0.035% (37/105,800) of European chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs19995237 7). Although this variant has been seen in the general population, its frequency is low enough to be consistent with a recessive carrier frequency. This nonsens e variant leads to a premature termination codon at position 641 which is predic ted to lead to a truncated or absent protein. In summary, although additional st udies are required to fully establish its clinical significance, the p.Leu641X variant is likely pathogenic for cranioectodermal dysplasia in an autosomal rece ssive manner. ACMG/AMP Criteria applied: PVS1_Strong, PS3_Supporting, PM3_Suppor ting. |
Gene |
RCV001557398 | SCV001779153 | likely pathogenic | not provided | 2024-06-14 | criteria provided, single submitter | clinical testing | Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 34490615, 25914204, 28332779, 22486404, 31980526, 34426522, 31589614, 34421506, 38161384, 35875935, 29068549, 33421337, 37895316, 38792657) |
Revvity Omics, |
RCV001557398 | SCV002020898 | pathogenic | not provided | 2021-10-14 | criteria provided, single submitter | clinical testing | |
Baylor Genetics | RCV000055830 | SCV004041065 | pathogenic | Cranioectodermal dysplasia 2 | 2023-05-26 | criteria provided, single submitter | clinical testing | |
Ce |
RCV001557398 | SCV004138649 | pathogenic | not provided | 2022-12-01 | criteria provided, single submitter | clinical testing | WDR35: PVS1, PS4:Moderate |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000288028 | SCV005039172 | pathogenic | WDR35-related disorder | 2024-03-25 | criteria provided, single submitter | clinical testing | Variant summary: WDR35 c.1922T>G (p.Leu641X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant allele was found at a frequency of 0.00016 in 218956 control chromosomes. c.1922T>G has been reported in the literature in individuals affected with WDR35-Related Disorders (Li_2015). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication have been ascertained in the context of this evaluation (PMID: 25914204). ClinVar contains an entry for this variant (Variation ID: 65619). Based on the evidence outlined above, the variant was classified as pathogenic. |
Dan Cohn Lab, |
RCV000515864 | SCV000612057 | pathogenic | Jeune thoracic dystrophy | 2017-06-01 | no assertion criteria provided | research | |
OMIM | RCV000055830 | SCV000680477 | pathogenic | Cranioectodermal dysplasia 2 | 2018-03-30 | no assertion criteria provided | literature only | |
University of Washington Center for Mendelian Genomics, |
RCV000515864 | SCV001480004 | likely pathogenic | Jeune thoracic dystrophy | no assertion criteria provided | research |