Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000465715 | SCV000541284 | pathogenic | Parathyroid carcinoma | 2024-07-30 | criteria provided, single submitter | clinical testing | This sequence change affects a donor splice site in intron 2 of the CDC73 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in CDC73 are known to be pathogenic (PMID: 12434154). This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individual(s) with primary hyperparathyroidism (PMID: 14985403, 23293331). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 403882). Studies have shown that disruption of this splice site alters mRNA splicing and is expected to lead to the loss of protein expression (PMID: 19332451). For these reasons, this variant has been classified as Pathogenic. |