Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001026298 | SCV001188648 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-01-28 | criteria provided, single submitter | clinical testing | The p.Y245H variant (also known as c.733T>C), located in coding exon 7 of the BMPR1A gene, results from a T to C substitution at nucleotide position 733. The tyrosine at codon 245 is replaced by histidine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Color Diagnostics, |
RCV001026298 | SCV001346650 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-01-03 | criteria provided, single submitter | clinical testing | This missense variant replaces tyrosine with histidine at codon 245 of the BMPR1A protein. Computational prediction tool 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. |
| Invitae | RCV001862364 | SCV002170571 | uncertain significance | Juvenile polyposis syndrome | 2021-12-27 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). This sequence change replaces tyrosine, which is neutral and polar, with histidine, which is basic and polar, at codon 245 of the BMPR1A protein (p.Tyr245His). This variant has not been reported in the literature in individuals affected with BMPR1A-related conditions. 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 expected to disrupt BMPR1A protein function. ClinVar contains an entry for this variant (Variation ID: 826976). |