ClinVar Miner

Submissions for variant NM_002878.3(RAD51D):c.556C>T (p.Arg186Ter) (rs387906843)

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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000129358 SCV000184122 pathogenic Hereditary cancer-predisposing syndrome 2017-09-27 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
Color RCV000129358 SCV000537684 pathogenic Hereditary cancer-predisposing syndrome 2016-03-07 criteria provided, single submitter clinical testing
Counsyl RCV000023220 SCV000488558 pathogenic Breast-ovarian cancer, familial 4 2016-06-09 criteria provided, single submitter clinical testing
GeneDx RCV000479705 SCV000567797 pathogenic not provided 2018-11-20 criteria provided, single submitter clinical testing This pathogenic variant is denoted RAD51D c.556C>T at the cDNA level and p.Arg186Ter (R186X) at the protein level. The substitution creates a nonsense variant, which changes an Arginine to a premature stop codon (CGA>TGA), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant has been observed in several individuals with a personal and family history of breast or ovarian cancer (Loveday 2011, Osher 2012, Baker 2015, Song 2015, Byers 2016). We consider this variant to be pathogenic.
Integrated Genetics/Laboratory Corporation of America RCV000589947 SCV000698107 pathogenic Hereditary breast and ovarian cancer syndrome 2016-09-30 criteria provided, single submitter clinical testing Variant summary: The RAD51D c.556C>T (p.Arg186X) variant results in a premature termination codon, predicted to cause a truncated or absent RAD51D protein due to nonsense mediated decay, which are commonly known mechanisms for disease. A truncation located downstream of this position have been classified as pathogenic by our laboratory (e.g. p.Arg232X). Mutation taster predicts a damaging outcome for this variant. This variant was found in 6/115838 control chromosomes at a frequency of 0.0000518, which does not exceed the estimated maximal expected allele frequency of a pathogenic RAD51D variant (0.000125). It was reported in several breast and ovarian cancer patients indicating causality. In addition multiple clinical diagnostic laboratories classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.
Invitae RCV000023220 SCV000287716 pathogenic Breast-ovarian cancer, familial 4 2019-01-09 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg186*) in the RAD51D gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs387906843, ExAC 0.01%). This variant has been reported in individuals and families affected with ovarian and breast cancer (PMID: 21822267, 25445424, 23372765, 26261251, 22415235). ClinVar contains an entry for this variant (Variation ID: 30285). Loss-of-function variants in RAD51D are known to be pathogenic (PMID: 21822267). For these reasons, this variant has been classified as Pathogenic.
Mendelics RCV000589947 SCV000839182 pathogenic Hereditary breast and ovarian cancer syndrome 2018-07-02 criteria provided, single submitter clinical testing
OMIM RCV000023220 SCV000044511 risk factor Breast-ovarian cancer, familial 4 2011-08-07 no assertion criteria provided literature only
PreventionGenetics RCV000479705 SCV000806579 pathogenic not provided 2016-11-02 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000479705 SCV000889827 pathogenic not provided 2017-10-26 criteria provided, single submitter clinical testing

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