ClinVar Miner

Submissions for variant NM_002878.3(RAD51D):c.413A>G (p.Asn138Ser) (rs201676898)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000212959 SCV000149724 uncertain significance not provided 2021-06-17 criteria provided, single submitter clinical testing Observed in individuals with a personal or family history including breast, ovarian, prostate, and other cancers (Johnson 2014, Ring 2016, Tung 2015, Shindo 2017, Sanchez-Bermudez 2018, Tsaousis 2019); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 25186627, 28767289, 25111073, 27443514, 29409816, 31159747, 21111057, 14704354, 19327148, 27535533)
Ambry Genetics RCV000115815 SCV000185137 likely benign Hereditary cancer-predisposing syndrome 2019-02-16 criteria provided, single submitter clinical testing In silico models in agreement (benign);Insufficient or conflicting evidence;Other strong data supporting benign classification
Invitae RCV000232930 SCV000287711 likely benign Breast-ovarian cancer, familial 4 2020-12-08 criteria provided, single submitter clinical testing
Counsyl RCV000232930 SCV000488855 uncertain significance Breast-ovarian cancer, familial 4 2016-07-05 criteria provided, single submitter clinical testing
GeneKor MSA RCV000115815 SCV000822179 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-01 criteria provided, single submitter clinical testing
Color Health, Inc RCV000115815 SCV000910644 likely benign Hereditary cancer-predisposing syndrome 2014-12-23 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001582579 SCV001821358 likely benign not specified 2021-08-23 criteria provided, single submitter clinical testing Variant summary: RAD51D c.413A>G (p.Asn138Ser) results in a conservative amino acid change located in the AAA+ ATPase domain of the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00012 in 251474 control chromosomes, predominantly at a frequency of 0.00055 within the Latino subpopulation in the gnomAD database. The observed variant frequency within Latino control individuals in the gnomAD database is approximately 4 fold of the estimated maximal expected allele frequency for a pathogenic variant in RAD51D causing Hereditary Breast And Ovarian Cancer Syndrome phenotype (0.00013), strongly suggesting that the variant is a benign polymorphism found primarily in populations of Latino origin. c.413A>G has been reported in the literature in individuals affected with Hereditary Breast And Ovarian Cancer Syndrome, prostate cancer, endometrial carcinoma, or pancreatic cancer (e.g. Johnson_2014, Tung_2015, Ring_2016, Shindo_2017, Sanchez-Bermudez_2018, Tsaousis_2019). These reports do not provide unequivocal conclusions about association of the variant with Hereditary Breast And Ovarian Cancer Syndrome. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Five clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Multiple laboratories reported the variant with conflicting assessments (likely benign n=2, VUS n=3). Based on the evidence outlined above, the variant was classified as likely benign.

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