ClinVar Miner

Submissions for variant NM_005732.4(RAD50):c.687del (p.Ser229fs)

gnomAD frequency: 0.00042  dbSNP: rs760146707
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
Ambry Genetics RCV000164362 SCV000214996 pathogenic Hereditary cancer-predisposing syndrome 2023-04-28 criteria provided, single submitter clinical testing The c.687delT pathogenic mutation, located in coding exon 5 of the RAD50 gene, results from a deletion of one nucleotide at nucleotide position 687, causing a translational frameshift with a predicted alternate stop codon (p.S229Rfs*6). This alteration was first reported in 2/151 Finnish familial breast/ovarian cancer individuals as well as in 6/1000 cancer free controls (Heikkinen K, J. Med. Genet. 2003 Dec; 40(12):e131). In a case control study of 317 consecutive newly diagnosed Finnish breast cancer patients and 1000 geographically matched healthy controls, eight breast cancer patients and six controls were carriers (95% CI 1.5–12.5, P = 0.008). Haplotype analysis suggests this is a Finnish founder mutation (Heikkinen K, Carcinogenesis 2006 Aug; 27(8):1). 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.
Counsyl RCV000409900 SCV000488545 likely pathogenic Nijmegen breakage syndrome-like disorder 2016-06-13 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000164362 SCV000628316 pathogenic Hereditary cancer-predisposing syndrome 2024-05-07 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Ser229Argfs*6) 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 (rs760146707, gnomAD 0.4%), and has an allele count higher than expected for a pathogenic variant. This premature translational stop signal has been observed in individual(s) with hereditary breast and ovarian cancer in that population (PMID: 14684699, 16385572, 16474176, 25452441). It is commonly reported in individuals of Finnish ancestry (PMID: 14684699, 16385572, 16474176, 25452441). ClinVar contains an entry for this variant (Variation ID: 185010). Algorithms developed to predict the effect of variants on gene product structure and function are not available or were not evaluated for this variant. Experimental studies have shown that this premature translational stop signal affects RAD50 function (PMID: 14684699, 16385572, 16474176). For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics RCV000409900 SCV004207437 pathogenic Nijmegen breakage syndrome-like disorder 2022-06-15 criteria provided, single submitter clinical testing

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.