Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV001011648 | SCV001171994 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-02-28 | criteria provided, single submitter | clinical testing | The c.145+2_145+3insTT intronic variant, results from an insertion of two nucleotides (TT) between nucleotide position 145+2 and 145+3 after intron 1 of the RAD51C gene. In silico splice site analysis predicts that this alteration may weaken the native splice donor site. RNA studies have demonstrated that this alteration results in an incomplete splice defect; 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. |
Invitae | RCV001037369 | SCV001200779 | uncertain significance | Fanconi anemia complementation group O | 2023-05-25 | 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). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 819250). This variant has not been reported in the literature in individuals affected with RAD51C-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.0009%). This sequence change falls in intron 1 of the RAD51C gene. It does not directly change the encoded amino acid sequence of the RAD51C protein. It affects a nucleotide within the consensus splice site. |
Color Diagnostics, |
RCV001011648 | SCV001353937 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-08-26 | criteria provided, single submitter | clinical testing | This variant causes an insertion of two nucleotides in intron 1 splice donor site of the RAD51C gene. Splice site prediction tools predict that this variant may impact RNA splicing. This prediction has not been confirmed in published RNA studies. An external laboratory has reported that this variant does not result in significant abnormal splicing compared to non-carrier control samples (ClinVar Accession ID: SCV001171994.2). This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 2/251282 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |