Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000464787 | SCV000541287 | likely pathogenic | Parathyroid carcinoma | 2023-10-22 | criteria provided, single submitter | clinical testing | This sequence change falls in intron 13 of the CDC73 gene. It does not directly change the encoded amino acid sequence of the CDC73 protein. It affects a nucleotide within the consensus splice site. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with clinical features of hyperparathyroidism-jaw tumor syndrome (Invitae). ClinVar contains an entry for this variant (Variation ID: 403885). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that this variant is associated with altered splicing resulting in unknown protein product impact (Invitae). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
Gene |
RCV001805057 | SCV002050339 | uncertain significance | not provided | 2021-12-28 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (Lek et al., 2016); Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports a deleterious effect on splicing |
Ambry Genetics | RCV002365584 | SCV002625409 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-03-20 | criteria provided, single submitter | clinical testing | The c.1155-3A>G intronic variant results from an A to G substitution 3 nucleotides upstream from coding exon 14 in the CDC73 gene. This nucleotide position is highly conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is not predicted to have any significant effect on this splice acceptor/donor site; however, direct evidence is unavailable. Since supporting evidence is limited at this time, the clinical significance of this variant remains unclear. |