Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000573500 | SCV000663634 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-09-10 | criteria provided, single submitter | clinical testing | The c.1631_1635+1delACAAAG variant is located between coding exon 10 and intron 10 of the RAD50 gene. This variant results from a deletion of 6 nucleotides at positions 1631 to 1635+1. This deletion includes the canonical splice donor site, which makes it likely to have some effect on normal mRNA splicing. These nucleotide positions are generally well conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will result in the creation or strengthening of a novel splice donor site. RNA studies have demonstrated that this alteration results in a transcript predicted to lead to a protein with an in-frame deletion of two amino acids; however, the exact functional impact of the deleted amino acids are unknown at this time (Ambry internal data). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Invitae | RCV000573500 | SCV000753333 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-10-19 | criteria provided, single submitter | clinical testing | 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: 480403). This variant is also known as c.1631_1635+1del. This variant has not been reported in the literature in individuals affected with RAD50-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.06%). This variant, c.1630_1635del, results in the deletion of 2 amino acid(s) of the RAD50 protein (p.Asp544_Lys545del), but otherwise preserves the integrity of the reading frame. 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. |
Revvity Omics, |
RCV001783068 | SCV002019619 | pathogenic | Nijmegen breakage syndrome-like disorder | 2019-07-14 | criteria provided, single submitter | clinical testing |