Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000481968 | SCV000569587 | likely pathogenic | not provided | 2016-03-21 | criteria provided, single submitter | clinical testing | This variant alters the initiator Methionine codon, and the resultant protein would be described as “p.Met1?” to signify that it is not known if the loss of Met1 prevents all protein translation or if an abnormal protein is produced using an alternate Methionine codon. RAD51D c.2T>G has not been previously published as a pathogenic variant, nor has it been reported as a benign polymorphism to our knowledge. However, the adjacent variant RAD51D c.1A>T, which also results in p.Met1?, has been reported in an individual with a personal history of both breast and ovarian cancer (Gutierrez-Enriquez 2014). As RAD51D c.2T>G is predicted to alter normal protein production, it is considered a likely pathogenic variant. |
| Labcorp Genetics |
RCV001865452 | SCV002258167 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 4 | 2021-07-15 | criteria provided, single submitter | clinical testing | RNA analysis indicates that this variant does not impact mRNA splicing (PMID: 24130102). 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. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. ClinVar contains an entry for this variant (Variation ID: 420660). Disruption of the initiator codon has been observed in individual(s) with breast, ovarian, and/or colorectal cancer (PMID: 24130102, 26681312, 30322717). This variant is not present in population databases (ExAC no frequency). This sequence change affects the initiator methionine of the RAD51D mRNA. The next in-frame methionine is located at codon 16. |
| Ambry Genetics | RCV002436538 | SCV002748636 | pathogenic | Hereditary cancer-predisposing syndrome | 2022-01-27 | criteria provided, single submitter | clinical testing | The p.M1? pathogenic mutation (also known as c.2T>G) is located in coding exon 1 of the RAD51D gene and results from a T to G substitution at nucleotide position 2. This alters the methionine residue at the initiation codon (ATG). This amino acid position is highly conserved in available vertebrate species. Sequence variations that modify the initiation codon are expected to result in either loss of translation initiation, N-terminal truncation, or cause a shift in the mRNA reading frame. Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation. |
| German Consortium for Hereditary Breast and Ovarian Cancer, |
RCV003482146 | SCV004227958 | likely pathogenic | Hereditary breast ovarian cancer syndrome | 2024-01-05 | criteria provided, single submitter | curation | Initiation codon variant, Class 4. According to the ACMG standard criteria we chose these criteria: PVS1 (very strong pathogenic): Initiation codon, PS1 (medium pathogenic): Additional variants affecting the start codon also classified as class 4/5. Possible alternative start codon at position 16 but pathogenic variants in first 15 aa described in ovarian cancer patients in ClinVar, PM2 (supporting pathogenic): absent from controls |