ClinVar Miner

Submissions for variant NM_002878.3(RAD51D):c.698A>G (p.Glu233Gly) (rs28363284)

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Total submissions: 13
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000588832 SCV000604996 benign not provided 2017-06-08 criteria provided, single submitter clinical testing
Ambry Genetics RCV000128967 SCV000172849 benign Hereditary cancer-predisposing syndrome 2014-06-10 criteria provided, single submitter clinical testing
Color RCV000128967 SCV000292107 benign Hereditary cancer-predisposing syndrome 2014-11-26 criteria provided, single submitter clinical testing
Counsyl RCV000203773 SCV000488546 likely benign Breast-ovarian cancer, familial 4 2016-06-09 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000212967 SCV000859932 likely benign not specified 2018-03-13 criteria provided, single submitter clinical testing
GeneDx RCV000212967 SCV000171275 benign not specified 2013-09-09 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Illumina Clinical Services Laboratory,Illumina RCV000381915 SCV000401966 likely benign Breast and Ovarian Cancer Susceptibility 2016-06-14 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000588832 SCV000698112 benign not provided 2017-08-09 criteria provided, single submitter clinical testing Variant summary: The RAD51D c.698A>G (p.Glu233Gly) variant locatedin the DNA recombination and repair protein RAD51-like, C-terminal domain (via InterPro) involves the alteration of a conserved nucleotide and 3/4 in silico tools predict a damaging outcome for this variant (SNPsandGO not captured due to low reliability index). This variant was found in 2670/277696 control chromosomes, predominantly observed in the European (Non-Finnish) subpopulation at a frequency of 0.0164 (2034/124022, 20 homozygotes). This frequency is about 131 times the estimated maximal expected allele frequency of a pathogenic RAD51D variant (0.000125), suggesting this is likely a benign polymorphism found primarily in the populations of European (Non-Finnish) origin. Multiple case-control studies also showed that this variant does not confer an increased risk to breast or ovarian cancer (Rodrguez-Lpez 2004, Dowty 2008, Jara 2010, Loveday 2011). Although, the variant was shown to confer a slight increased risk for breast cancer in the BRCA-negative only with BrC cases (p-value = 0.02), this finding was not reproducible in a second study in Chilean BRCA1/2 negative women with a positive family history of breast cancer (Rodrguez-Lpez 2004, Jara 2010). Several in-vitro studies on human cancer cell lines, RAD51D-deficient mouse embryonic fibroblasts, and Yeast two-hybrid analysis have reported increased resistance to DNA-damaging agents, increased cellular proliferation, and decreased interaction with RAD51C (Nadkarni_2009). However, these experimental models are generally considered as weak experimental evidence as it is not clear if the results and conclusions drawn from these studies are applicable to the mechanism and presentation of disease. Two computational studies reporting an effect of this variant on function provide conflicting results (Rodrguez-Lpez 2004 and Zhao_2014). In addition, multiple clinical diagnostic laboratories have classified the variant as likely benign/benign. Furthermore, multiple internal LCA samples report the variant to co-occur with another pathogenic variant: PALB2 - c.196C>T (p.Gln66X), MUTYH - c.1187G>A (p.Gly396Asp), BARD1 - c.1690C>T (p.Gln564X), and likely pathogenic, TP53, c.782+1G>T. Therefore, due to the high occurrence in controls, co-occurrences with another pathogenic variant, and no strong established associated risk, the variant of interest has been classified as benign".
Invitae RCV000203773 SCV000262197 benign Breast-ovarian cancer, familial 4 2017-08-18 criteria provided, single submitter clinical testing
PreventionGenetics RCV000212967 SCV000806585 benign not specified 2016-11-04 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000212967 SCV000602166 benign not specified 2017-05-18 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000588832 SCV000889832 benign not provided 2017-05-18 criteria provided, single submitter clinical testing
True Health Diagnostics RCV000128967 SCV000788209 benign Hereditary cancer-predisposing syndrome 2018-01-12 no assertion criteria provided clinical testing

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