ClinVar Miner

Submissions for variant NM_005732.4(RAD50):c.2173C>T (p.Arg725Trp) (rs369560280)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000131653 SCV000186680 uncertain significance Hereditary cancer-predisposing syndrome 2017-11-03 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Integrated Genetics/Laboratory Corporation of America RCV000780661 SCV000918119 likely benign not specified 2018-01-02 criteria provided, single submitter clinical testing Variant summary: The RAD50 c.2173C>T (p.Arg725Trp) variant involves the alteration of a conserved nucleotide that is located in the RAD50, zinc hook domain (InterPro). 3/3 in silico tools predict a damaging outcome for this variant (SNPsandGO not captured due to low reliability index). This variant was found in 55/275042 control chromosomes, predominantly observed in the Latino subpopulation at a frequency of 0.001541 (53/34384). This frequency is about 25 times the estimated maximal expected allele frequency of a pathogenic RAD50 variant (0.0000625), suggesting this is likely a benign polymorphism found primarily in the populations of Latino origin. The variant has been cited in the literature, though it is unclear whether it was identified in breast cancer cases or control individuals (Damiola_2014; Young_2016). Two clinical diagnostic laboratories/reputable databases classified this variant as one of uncertain significance. Taken together, this variant is classified as likely benign.
Invitae RCV000131653 SCV000289031 uncertain significance Hereditary cancer-predisposing syndrome 2018-12-26 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 725 of the RAD50 protein (p.Arg725Trp). The arginine residue is moderately conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is present in population databases (rs369560280, ExAC 0.1%). This variant has been reported in individuals affected with breast cancer (PMID: 24894818). ClinVar contains an entry for this variant (Variation ID: 142505). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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.

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.