Total submissions: 24
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000212965 | SCV000149728 | pathogenic | not provided | 2023-05-26 | criteria provided, single submitter | clinical testing | Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); Observed in individuals with RAD51D-related cancers (Gutierrez-Enriquez et al., 2014; Wickramanayake et al., 2012; Janatova et al., 2015; Gonzalez-Rivera et al., 2016; Lilyquist et al., 2017; Tedaldi et al., 2017; Sanchez-Bermudez et al., 2018; Suszynska et al., 2020; Hauke et al., 2021); This variant is associated with the following publications: (PMID: 28423363, 28985766, 25445424, 24130102, 22986143, 26057125, 26720728, 27083178, 26681312, 29409816, 29470806, 24240112, 31589614, 32295079, 26689913, 30306255, 32318955, 32107557, 32359370, 29522266, 32980694, 34923718, 28888541, 35264596, 35565380, 33804961, 34308104) |
Ambry Genetics | RCV000115819 | SCV000185867 | pathogenic | Hereditary cancer-predisposing syndrome | 2022-07-20 | criteria provided, single submitter | clinical testing | The p.R232* pathogenic mutation (also known as c.694C>T), located in coding exon 8 of the RAD51D gene, results from a C to T substitution at nucleotide position 694. This changes the amino acid from an arginine to a stop codon within coding exon 8. This mutation has been identified in several patients diagnosed with ovarian carcinoma with a family history of breast and/or ovarian cancer (Wickramanayake A et al. Gynecol. Oncol. 2012 Dec;127:552-5; Gutiérrez-Enríquez S et al. Int. J. Cancer. 2014 May;134:2088-97; Sánchez-Bermúdez AI et al. Eur J Med Genet 2018 Jun;61:355-361). It was also observed in two Czech women with high-grade serous adenocarcinoma diagnosed under the age of 45 with no family history of malignancy; in one woman with a personal history of triple negative breast cancer; and in one woman with a personal history of DCIS at age 47 and ovarian cancer at age 54 (Janatova M et al. PLoS ONE. 2015 Jun;10:e0127711; Gonzalez-Rivera M et al. Breast Cancer Res. Treat. 2016 04;156:507-515; Tedaldi G et al. Oncotarget. 2017 Jul;8:47064-4707). One study has estimated ovarian cancer risk for this variant (OR 16.07, 95% of 5.12-50.46; p value <0.0001) (Suszynska M et al. J Ovarian Res, 2020 May;13:50). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. |
Color Diagnostics, |
RCV000115819 | SCV000292163 | pathogenic | Hereditary cancer-predisposing syndrome | 2022-08-15 | criteria provided, single submitter | clinical testing | This variant changes 1 nucleotide in exon 8 of the RAD51D gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been observed in individuals affected with ovarian cancer (PMID: 22986143, 24130102, 26057125, 28423363). In a large breast cancer case-control study, this variant was identified in 12/60454 cases and 5/53456 controls; OR=2.122 (95%CI 0.748 to 6.024); p-value=0.223 (PMID: 33471991 - Leiden Open Variation Database DB-ID RAD51D_000003). This variant has been identified in 4/277224 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Loss of RAD51D function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic. |
Counsyl | RCV000410860 | SCV000488995 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 4 | 2016-08-02 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV000410860 | SCV000551331 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 4 | 2024-01-27 | 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. Loss-of-function variants in RAD51D are known to be pathogenic (PMID: 21822267). This variant is present in population databases (rs587780104, gnomAD 0.004%). This premature translational stop signal has been observed in individual(s) with breast cancer and ovarian cancer (PMID: 22986143, 24130102, 26057125, 26681312, 27083178, 28423363). ClinVar contains an entry for this variant (Variation ID: 127893). RNA analysis performed to evaluate the impact of this premature translational stop signal on mRNA splicing indicates it does not significantly alter splicing (Invitae). For these reasons, this variant has been classified as Pathogenic. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000586822 | SCV000698111 | pathogenic | Hereditary breast ovarian cancer syndrome | 2019-04-04 | criteria provided, single submitter | clinical testing | Variant summary: RAD51D c.694C>T (p.Arg232X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (eg. c.748delC, p.His250fsX2). The variant allele was found at a frequency of 1.8e-05 in 274154 control chromosomes. c.694C>T has been reported in the literature in multiple individuals affected with Hereditary Breast and Ovarian Cancer (Wickramanayake_2012, Gutierrez-Enriquez_2014, Janatova_2015, Gonzalez-Rivera_2016, Tedaldi_2017). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Eight clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
Mendelics | RCV000586822 | SCV000839180 | pathogenic | Hereditary breast 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, |
RCV000410860 | SCV000894110 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 4 | 2018-10-31 | criteria provided, single submitter | clinical testing | |
Institute of Human Genetics, |
RCV000410860 | SCV001440050 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 4 | 2024-11-05 | criteria provided, single submitter | clinical testing | Criteria applied: PVS1,PS4_MOD,PM2_SUP |
Ce |
RCV000212965 | SCV001961679 | pathogenic | not provided | 2024-04-01 | criteria provided, single submitter | clinical testing | RAD51D: PVS1, PM2, PS4:Moderate |
Institute for Clinical Genetics, |
RCV000212965 | SCV002010052 | pathogenic | not provided | 2021-11-03 | criteria provided, single submitter | clinical testing | |
Sema4, |
RCV000115819 | SCV002534844 | pathogenic | Hereditary cancer-predisposing syndrome | 2021-07-16 | criteria provided, single submitter | curation | |
MGZ Medical Genetics Center | RCV000410860 | SCV002580679 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 4 | 2022-01-31 | criteria provided, single submitter | clinical testing | |
Human Genetics Bochum, |
RCV002463640 | SCV002758607 | pathogenic | Colorectal cancer | 2022-01-04 | criteria provided, single submitter | clinical testing | ACMG criteria used to clasify this variant: PVS1, PS4, PM2 |
Laboratory of Medical Genetics Unit, |
RCV003313779 | SCV004012919 | likely pathogenic | Diffuse midline glioma, H3 K27-altered | 2020-10-08 | criteria provided, single submitter | research | |
Myriad Genetics, |
RCV000410860 | SCV004017753 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 4 | 2023-04-06 | criteria provided, single submitter | clinical testing | This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation. |
Baylor Genetics | RCV000410860 | SCV004208076 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 4 | 2024-03-28 | criteria provided, single submitter | clinical testing | |
Juno Genomics, |
RCV000410860 | SCV005417194 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 4 | criteria provided, single submitter | clinical testing | PM2_Supporting+PVS1+PS4_Moderate | |
German Consortium for Hereditary Breast and Ovarian Cancer, |
RCV000785237 | SCV000923805 | pathogenic | Ovarian neoplasm | 2018-12-01 | no assertion criteria provided | research | |
CZECANCA consortium | RCV001271051 | SCV001451870 | pathogenic | Breast and/or ovarian cancer | 2019-06-11 | no assertion criteria provided | clinical testing | |
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, |
RCV000212965 | SCV001959919 | pathogenic | not provided | no assertion criteria provided | clinical testing | ||
Clinical Genetics DNA and cytogenetics Diagnostics Lab, |
RCV000212965 | SCV001973407 | pathogenic | not provided | no assertion criteria provided | clinical testing | ||
Laboratory for Genotyping Development, |
RCV003162542 | SCV002758191 | pathogenic | Gastric cancer | 2021-07-01 | no assertion criteria provided | research |