Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Color Diagnostics, |
RCV001185507 | SCV001351737 | likely benign | Hereditary cancer-predisposing syndrome | 2019-12-14 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV001505424 | SCV001710330 | likely benign | Fanconi anemia complementation group O | 2024-03-14 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000929068 | SCV001758923 | likely benign | not provided | 2018-07-30 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV001185507 | SCV002629275 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-04-25 | criteria provided, single submitter | clinical testing | The c.405-5G>A intronic variant results from a G to A substitution 5 nucleotides upstream from coding exon 3 in the RAD51C gene. This nucleotide position is not well conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will not have any significant effect on splicing. Based on the available evidence, the clinical significance of this variant remains unclear. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV003226408 | SCV003923240 | uncertain significance | not specified | 2023-03-13 | criteria provided, single submitter | clinical testing | Variant summary: RAD51C c.405-5G>A alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 4/4 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant was absent in 251472 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.405-5G>A in individuals affected with Hereditary Breast And Ovarian Cancer Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Five submitters have provided clinical-significance assessments for this variant to ClinVar after 2014, and classified it as likely benign (n=4) or uncertain significance (n=1). Based on the evidence outlined above, the variant was classified as uncertain significance. |