Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Color Diagnostics, |
RCV000584627 | SCV000691311 | likely benign | Hereditary cancer-predisposing syndrome | 2017-04-24 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV000696813 | SCV000825392 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 4 | 2022-11-15 | criteria provided, single submitter | clinical testing | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown this variant is associated with skipping of exon 3, but one or more of the resulting mRNA isoform(s) may be naturally occurring (PMID: 30623411; Invitae). ClinVar contains an entry for this variant (Variation ID: 492412). This variant has not been reported in the literature in individuals affected with RAD51D-related conditions. This variant is present in population databases (rs201974522, gnomAD 0.007%). This sequence change falls in intron 2 of the RAD51D gene. It does not directly change the encoded amino acid sequence of the RAD51D protein. It affects a nucleotide within the consensus splice site. |
Ambry Genetics | RCV000584627 | SCV002698217 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-11-19 | criteria provided, single submitter | clinical testing | The c.145-3C>T intronic variant results from a C to T substitution 3 nucleotides upstream from coding exon 3 in the RAD51D gene. This nucleotide position is well conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will not have any significant effect on splicing. RNA studies have demonstrated that this alteration results in an incomplete splice defect involving exons excluded from naturally occurring transcripts; the clinical impact of this abnormal splicing is unknown at this time (Ambry internal data). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |