Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Color Diagnostics, |
RCV001189226 | SCV001356480 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-12-10 | criteria provided, single submitter | clinical testing | This missense variant replaces aspartic acid with glycine at codon 211 of the BMPR1A protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified 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. |
Ambry Genetics | RCV001189226 | SCV002654671 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-10-28 | criteria provided, single submitter | clinical testing | The p.D211G variant (also known as c.632A>G), located in coding exon 6 of the BMPR1A gene, results from an A to G substitution at nucleotide position 632. The aspartic acid at codon 211 is replaced by glycine, an amino acid with similar properties. This amino acid position is conserved. 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. |
Invitae | RCV002560042 | SCV003215201 | uncertain significance | Juvenile polyposis syndrome | 2022-07-02 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with BMPR1A-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 211 of the BMPR1A protein (p.Asp211Gly). ClinVar contains an entry for this variant (Variation ID: 926551). 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. 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 not expected to disrupt BMPR1A protein function. |