Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Color Diagnostics, |
RCV001177711 | SCV001341973 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-12-04 | criteria provided, single submitter | clinical testing | This missense variant replaces aspartic acid with glutamic acid at codon 40 of the BMPR1A protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with BMPR1A-related disorders 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 | RCV001177711 | SCV002647969 | uncertain significance | Hereditary cancer-predisposing syndrome | 2015-12-10 | criteria provided, single submitter | clinical testing | The p.D40E variant (also known as c.120C>A), located in coding exon 2 of the BMPR1A gene, results from a C to A substitution at nucleotide position 120. The aspartic acid at codon 40 is replaced by glutamic acid, an amino acid with highly similar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6503 samples (13006 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.002% (greater than 65000 alleles tested) in our clinical cohort. Based on protein sequence alignment, this amino acid position is not well conserved in available vertebrate species, and glucine is the reference amino acid in several mammals. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of p.D40E remains unclear. |