ClinVar Miner

Submissions for variant NM_005732.4(RAD50):c.832C>T (p.Arg278Ter)

gnomAD frequency: 0.00002  dbSNP: rs766315644
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000476546 SCV000548064 pathogenic Hereditary cancer-predisposing syndrome 2024-01-10 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg278*) in the RAD50 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in RAD50 are known to be pathogenic (PMID: 19409520). This variant is present in population databases (rs766315644, gnomAD 0.01%). This premature translational stop signal has been observed in individual(s) with breast cancer (PMID: 25452441). ClinVar contains an entry for this variant (Variation ID: 408402). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV000476546 SCV000663604 pathogenic Hereditary cancer-predisposing syndrome 2023-04-28 criteria provided, single submitter clinical testing The p.R278* pathogenic mutation (also known as c.832C>T), located in coding exon 6 of the RAD50 gene, results from a C to T substitution at nucleotide position 832. This changes the amino acid from an arginine to a stop codon within coding exon 6. This mutation has been detected in 1/1824 patients with triple negative breast cancer who were unselected for a family history of breast or ovarian cancer (Couch FJ et al. J. Clin. Oncol. 2015 Feb;33:304-11) as well as 1/615 unselected patients with a pancreatic exocrine neoplasm (Lower MA et al. J. Natl. Cancer Inst. 2018 Oct;110(10):1067-1074). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Baylor Genetics RCV003463903 SCV004207332 pathogenic Nijmegen breakage syndrome-like disorder 2023-09-26 criteria provided, single submitter clinical testing
GenomeConnect - Invitae Patient Insights Network RCV003483622 SCV004228484 not provided not provided no assertion provided phenotyping only Variant interpreted as Uncertain significance and reported on 10-08-2015 by Lab Ambry Genetics. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.