Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Color Diagnostics, |
RCV000583256 | SCV000691330 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-04-03 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV000583256 | SCV001181826 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-06-10 | criteria provided, single submitter | clinical testing | The c.345G>A variant (also known as p.Q115Q), located in coding exon 4 of the RAD51D gene, results from a G to A substitution at nucleotide position 345. This nucleotide substitution does not change the amino acid at codon 115. However, this change occurs in the last base pair of coding exon 4, which makes it likely to have some effect on normal mRNA splicing. This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice donor site. Internal RNA studies as well as in the literature have shown that exons 3 through 5 are excluded in several naturally occurring RAD51D transcripts (Davy G et al. Eur. J. Hum. Genet., 2017 10;25:1147-1154; Ambry internal data). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
German Consortium for Hereditary Breast and Ovarian Cancer, |
RCV003483683 | SCV004228286 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2024-01-08 | criteria provided, single submitter | curation | Own splice analysis not quantitative. Quantitative splice analysis and segregation data needed. According to the ACMG standard criteria we chose these criteria: PS3 (strong pathogenic): Enhanced skipping of exon 4 in RNA-analysis. Quantification not possible., PM2 (supporting pathogenic): not in gnomAD, PP3 (supporting pathogenic): PP3 (spliceAI: RAD51D: 0.9) |
Myriad Genetics, |
RCV004024644 | SCV004933564 | likely pathogenic | Breast-ovarian cancer, familial, susceptibility to, 4 | 2024-01-04 | criteria provided, single submitter | clinical testing | This variant is considered likely pathogenic. mRNA analysis has demonstrated abnormal mRNA splicing occurs [Myriad internal data]. |