Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Center for Genomic Medicine, |
RCV005231296 | SCV005872521 | pathogenic | not provided | 2025-03-04 | criteria provided, single submitter | clinical testing | Classification criteria: PVS1, PM2_sup, PS3_sup |
| Myriad Genetics, |
RCV000703444 | SCV004930447 | likely pathogenic | Breast-ovarian cancer, familial, susceptibility to, 4 | 2024-01-05 | criteria provided, single submitter | clinical testing | This variant is considered likely pathogenic. This variant occurs within a consensus splice junction and is predicted to result in abnormal mRNA splicing of either an out-of-frame exon or an in-frame exon necessary for protein stability and/or normal function. |
| Ambry Genetics | RCV001026354 | SCV001188717 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2020-01-02 | criteria provided, single submitter | clinical testing | The c.738+1G>A intronic variant results from a G to A substitution one nucleotide after coding exon 8 of the RAD51D gene. This alteration was identified in a patient diagnosed with high-grade serous ovarian cancer (Konstanta I et al. J. Hum. Genet., 2018 Nov;63:1149-1158). RNA analyses have shown that this alteration produces an abnormal transcript with partial retention of 37 intronic bases, resulting in a predicted frameshift and premature termination codon (Konstanta I et al. J. Hum. Genet., 2018 Nov;63:1149-1158, Ambry internal data). This nucleotide position is highly conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is predicted to abolish the native splice donor site. Alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. As such, this alteration is classified as likely pathogenic. |
| Labcorp Genetics |
RCV000703444 | SCV000832343 | likely pathogenic | Breast-ovarian cancer, familial, susceptibility to, 4 | 2022-01-11 | criteria provided, single submitter | clinical testing | This sequence change affects a donor splice site in intron 8 of the RAD51D gene. RNA analysis indicates that disruption of this splice site induces altered splicing and may result in an absent or disrupted protein product. This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individual(s) with ovarian cancer (PMID: 30111881). ClinVar contains an entry for this variant (Variation ID: 580022). Studies have shown that disruption of this splice site results in partial retention of 37 nucleotides from intron 8 and introduces a premature termination codon (PMID: 30111881). The resulting mRNA is expected to undergo nonsense-mediated decay. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |