Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000691580 | SCV000819366 | pathogenic | Cranioectodermal dysplasia 2; Short-rib thoracic dysplasia 7 with or without polydactyly | 2023-01-23 | criteria provided, single submitter | clinical testing | This sequence change affects codon 1126 of the WDR35 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the WDR35 protein. RNA analysis indicates that this variant induces altered splicing and may result in an absent or disrupted protein product. This variant is present in population databases (rs746128772, gnomAD 0.004%). This variant has been observed in individual(s) with Ellis-van Creveld syndrome and/or Sensenbrenner syndrome (PMID: 25908617, 33606107). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 570668). Studies have shown that this variant results in skipping of exon 27 and introduces a premature termination codon (PMID: 25908617). The resulting mRNA is expected to undergo nonsense-mediated decay. For these reasons, this variant has been classified as Pathogenic. |
Baylor Genetics | RCV003333099 | SCV004040638 | pathogenic | Cranioectodermal dysplasia 2 | 2023-05-26 | criteria provided, single submitter | clinical testing |