Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000164416 | SCV000215054 | pathogenic | Hereditary cancer-predisposing syndrome | 2022-05-25 | criteria provided, single submitter | clinical testing | The c.2517dupA pathogenic mutation, located in coding exon 15 of the RAD50 gene, results from a duplication of A at nucleotide position 2517, causing a translational frameshift with a predicted alternate stop codon (p.D840Rfs*5). This mutation was reported in 1/392 BRCA1/2-negative Spanish breast cancer patients (Tavera-Tapia A et al. Breast Cancer Res. Treat. 2017 02;161:597-604). 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. |
| Invitae | RCV000164416 | SCV000547965 | pathogenic | Hereditary cancer-predisposing syndrome | 2023-09-29 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Asp840Argfs*5) in the RAD50 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in RAD50 are known to be pathogenic (PMID: 19409520). This variant is present in population databases (rs786201897, gnomAD 0.006%). This premature translational stop signal has been observed in individual(s) with breast and/or ovarian cancer (PMID: 27913932). ClinVar contains an entry for this variant (Variation ID: 185058). For these reasons, this variant has been classified as Pathogenic. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003155095 | SCV003845034 | pathogenic | Hereditary breast ovarian cancer syndrome | 2023-02-20 | criteria provided, single submitter | clinical testing | Variant summary: RAD50 c.2517dupA (p.Asp840ArgfsX5) 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 in ClinVar. The variant allele was found at a frequency of 8e-06 in 251104 control chromosomes (gnomAD). c.2517dupA has been reported in the literature in individuals affected with Hereditary Breast And Ovarian Cancer Syndrome (Tavera-Tapia_2017, Miguel_2021). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two ClinVar submitters (evaluation after 2014) cite this variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
| Baylor Genetics | RCV003462134 | SCV004207417 | pathogenic | Nijmegen breakage syndrome-like disorder | 2023-03-03 | criteria provided, single submitter | clinical testing |