Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001321307 | SCV001512130 | uncertain significance | Parathyroid carcinoma | 2023-12-30 | criteria provided, single submitter | clinical testing | This sequence change affects codon 324 of the CDC73 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the CDC73 protein. This variant also falls at the last nucleotide of exon 10, which is part of the consensus splice site for this exon. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with CDC73-related conditions. ClinVar contains an entry for this variant (Variation ID: 1021527). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Ambry Genetics | RCV002377398 | SCV002692244 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-11-04 | criteria provided, single submitter | clinical testing | The c.972G>A variant (also known as p.T324T), located in coding exon 10 of the CDC73 gene, results from a G to A substitution at nucleotide position 972. This nucleotide substitution does not change the threonine at codon 324. However, this change occurs in the last base pair of coding exon 10, which makes it likely to have some effect on normal mRNA splicing. This nucleotide position is well conserved in available vertebrate species. In silico splice site analysis for this alteration is inconclusive. RNA studies have demonstrated that this alteration results in an incomplete splice defect; the clinical impact of this abnormal splicing is unknown at this time (Ambry internal data). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |