Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001384739 | SCV001584376 | pathogenic | not provided | 2022-07-15 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with C2CD3-related conditions. This sequence change creates a premature translational stop signal (p.Val332Glyfs*23) in the C2CD3 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in C2CD3 are known to be pathogenic (PMID: 24997988, 26477546). This variant is present in population databases (rs750700691, gnomAD 0.006%). ClinVar contains an entry for this variant (Variation ID: 1072108). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. For these reasons, this variant has been classified as Pathogenic. |
| Revvity Omics, |
RCV001780341 | SCV002022109 | likely pathogenic | Orofaciodigital syndrome type 14 | 2019-07-10 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001780341 | SCV005184594 | pathogenic | Orofaciodigital syndrome type 14 | 2024-05-24 | criteria provided, single submitter | clinical testing | Variant summary: C2CD3 c.994dupG (p.Val332GlyfsX23) results in a premature termination codon, predicted to cause absence of the protein due to nonsense mediated decay, which is a commonly known mechanism for disease. The variant allele was found at a frequency of 8e-06 in 251328 control chromosomes (gnomAD). To our knowledge, no occurrence of c.994dupG in individuals affected with Orofaciodigital Syndrome Type 14 and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 1072108). Based on the evidence outlined above, the variant was classified as pathogenic. |
| Gene |
RCV001384739 | SCV005414819 | likely pathogenic | not provided | 2024-05-24 | criteria provided, single submitter | clinical testing | Frameshift 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; Has not been previously published as pathogenic or benign to our knowledge |