ClinVar Miner

Submissions for variant NM_002878.3(RAD51D):c.694C>T (p.Arg232Ter) (rs587780104)

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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000212965 SCV000149728 pathogenic not provided 2018-03-28 criteria provided, single submitter clinical testing This pathogenic variant is denoted RAD51D c.694C>T at the cDNA level and p.Arg232Ter (R232X) 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. RAD51D Arg232Ter has been observed in several individuals with ovarian cancer, including those with a family history of breast and ovarian cancer, as well as in one individual with triple negative breast cancer (Wickramanayake 2012, Gutierrez-Enr?quez 2014, Janatova 2015, Gonz?lez-Rivera 2016, Tedaldi 2017, S?nchez-Berm?dez 2018). This variant is considered pathogenic.
Ambry Genetics RCV000115819 SCV000185867 pathogenic Hereditary cancer-predisposing syndrome 2018-02-06 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 RCV000115819 SCV000292163 pathogenic Hereditary cancer-predisposing syndrome 2015-02-13 criteria provided, single submitter clinical testing
Counsyl RCV000410860 SCV000488995 pathogenic Breast-ovarian cancer, familial 4 2016-08-02 criteria provided, single submitter clinical testing
Invitae RCV000410860 SCV000551331 pathogenic Breast-ovarian cancer, familial 4 2018-12-26 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg232*) in the RAD51D gene. It is expected to result in an absent or disrupted protein product. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has been observed in several individuals affected with ovarian cancer (PMID: 22986143, 24130102, 26057125, 28423363), as well as individuals with breast cancer (PMID: 27083178, 26681312, 28423363). ClinVar contains an entry for this variant (Variation ID: 127893). Loss-of-function variants in RAD51D are known to be pathogenic (PMID: 21822267). For these reasons, this variant has been classified as Pathogenic.
Integrated Genetics/Laboratory Corporation of America RCV000586822 SCV000698111 pathogenic Hereditary breast and ovarian cancer syndrome 2016-06-27 criteria provided, single submitter clinical testing Variant summary: The c.694C>T (p.Arg232*) variant in Rad51D gene is a nonsense change predicted cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay, which is a known disease mechanism in HBOC. The variant has been reported in multiple affected individuals presented with OvC. This variant is found in 1/93900 control chromosomes at a frequency of 0.00001, which does not exceed the maximal expected frequency of a pathogenic allele (0.00012) in this gene. Lastly, multiple reputable databases/diagnostic centers classified the variant of interest as Pathogenic. Taken together, the variant was classified as Pathogenic.
Mendelics RCV000586822 SCV000839180 pathogenic Hereditary breast and ovarian cancer syndrome 2018-07-02 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000212965 SCV000889830 pathogenic not provided 2018-03-07 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000410860 SCV000894110 pathogenic Breast-ovarian cancer, familial 4 2018-10-31 criteria provided, single submitter clinical testing
German Consortium for Hereditary Breast and Ovarian Cancer Center Cologne,University Hospital Cologne RCV000785237 SCV000923805 pathogenic Ovarian Neoplasms 2018-12-01 no assertion criteria provided research

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