Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001018268 | SCV001179482 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-02-03 | criteria provided, single submitter | clinical testing | The p.I292V variant (also known as c.874A>G), located in coding exon 8 of the BMPR1A gene, results from an A to G substitution at nucleotide position 874. The isoleucine at codon 292 is replaced by valine, 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. |
| Color Diagnostics, |
RCV001018268 | SCV001357277 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-01-21 | criteria provided, single submitter | clinical testing | This missense variant replaces isoleucine with valine at codon 292 of the BMPR1A protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 1/250794 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. |
| Labcorp Genetics |
RCV001207349 | SCV001378694 | uncertain significance | Juvenile polyposis syndrome | 2025-01-16 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 292 of the BMPR1A protein (p.Ile292Val). This variant is present in population databases (rs746800007, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with BMPR1A-related conditions. ClinVar contains an entry for this variant (Variation ID: 822701). Invitae Evidence Modeling incorporating data from in vitro experimental studies (internal data) indicates that this missense variant is not expected to disrupt BMPR1A function with a negative predictive value of 95%. 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. |
| Baylor Genetics | RCV003473583 | SCV004212607 | uncertain significance | Polyposis syndrome, hereditary mixed, 2 | 2023-08-29 | criteria provided, single submitter | clinical testing | |
| All of Us Research Program, |
RCV001207349 | SCV005424109 | uncertain significance | Juvenile polyposis syndrome | 2024-03-05 | criteria provided, single submitter | clinical testing | This missense variant replaces isoleucine with valine at codon 292 of the BMPR1A protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 1/250794 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. |