ClinVar Miner

Submissions for variant NM_002878.3(RAD51D):c.796C>T (p.Arg266Cys) (rs587781813)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000130084 SCV000184912 uncertain significance Hereditary cancer-predisposing syndrome 2017-11-02 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Color RCV000130084 SCV000686488 uncertain significance Hereditary cancer-predisposing syndrome 2018-07-23 criteria provided, single submitter clinical testing
Counsyl RCV000411407 SCV000489353 uncertain significance Breast-ovarian cancer, familial 4 2016-09-27 criteria provided, single submitter clinical testing
GeneDx RCV000255993 SCV000321930 uncertain significance not provided 2018-07-26 criteria provided, single submitter clinical testing This variant is denoted RAD51D c.796C>T at the cDNA level, p.Arg266Cys (R266C) at the protein level, and results in the change of an Arginine to a Cysteine (CGC>TGC). This variant has been reported in at least one woman with ovarian cancer and another with breast cancer (Thompson 2013, Hauke 2018). RAD51D Arg266Cys was observed at an allele frequency of 0.08% (24/30,782) in individuals of South Asian ancestry in large population cohorts (Lek 2016). This variant is located in the RAD51C binding domain (Miller 2004). In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect. Based on currently available evidence, it is unclear whether RAD51D Arg266Cys is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
GeneKor MSA RCV000130084 SCV000822184 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-01 criteria provided, single submitter clinical testing
GenomeConnect, ClinGen RCV000255993 SCV000986823 not provided not provided no assertion provided phenotyping only Variant interpretted as Uncertain significance and reported on 05/07/2018 by GTR ID Credit Valley Hospital Department of Laboratory Medicine. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.
Invitae RCV000411407 SCV000551380 uncertain significance Breast-ovarian cancer, familial 4 2018-06-19 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 266 of the RAD51D protein (p.Arg266Cys). The arginine residue is moderately conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs587781813, ExAC 0.08%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has been reported in the literature in an individual with a personal and/or family history of breast cancer (PMID: 23372765). ClinVar contains an entry for this variant (Variation ID: 141519). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.
PreventionGenetics RCV000255993 SCV000806588 uncertain significance not provided 2017-10-02 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000255993 SCV000888611 uncertain significance not provided 2018-01-13 criteria provided, single submitter clinical testing

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