Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001011580 | SCV001171917 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-11-22 | criteria provided, single submitter | clinical testing | The p.R480Q variant (also known as c.1439G>A), located in coding exon 10 of the BMPR1A gene, results from a G to A substitution at nucleotide position 1439. The arginine at codon 480 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV001800917 | SCV002046212 | uncertain significance | not provided | 2020-09-14 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV002551746 | SCV003309205 | uncertain significance | Juvenile polyposis syndrome | 2022-05-25 | 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. This variant disrupts the p.Arg480 amino acid residue in BMPR1A. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 18178612; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt BMPR1A protein function. ClinVar contains an entry for this variant (Variation ID: 819216). This missense change has been observed in individual(s) with breast cancer (PMID: 29338689). This variant is present in population databases (rs535109719, gnomAD 0.007%). This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 480 of the BMPR1A protein (p.Arg480Gln). |