Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000804983 | SCV000944924 | uncertain significance | Parathyroid carcinoma | 2023-09-03 | criteria provided, single submitter | clinical testing | This sequence change falls in intron 12 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. 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: 649933). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). RNA analysis performed to evaluate the impact of this variant on mRNA splicing indicates it does not significantly alter splicing (Invitae). 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 | RCV002406794 | SCV002721076 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-05-10 | criteria provided, single submitter | clinical testing | The c.1066+5G>A intronic variant results from a G to A substitution 5 nucleotides after coding exon 12 in the CDC73 gene. This nucleotide position is well conserved in available vertebrate species. In silico splice site analysis for this alteration is inconclusive; however, direct evidence is insufficient at this time (Ambry internal data). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Fulgent Genetics, |
RCV002495096 | SCV002800953 | uncertain significance | Hyperparathyroidism 1; Parathyroid carcinoma; Hyperparathyroidism 2 with jaw tumors | 2021-11-16 | criteria provided, single submitter | clinical testing |