Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001031401 | SCV001194707 | likely pathogenic | Generalized juvenile polyposis/juvenile polyposis coli | 2019-02-16 | criteria provided, single submitter | clinical testing | This variant is a gross deletion of the genomic region encompassing the promoter of the BMPR1A gene. The 5' end of this event is unknown as it extends beyond the assayed region for this gene, and therefore may encompass additional genes. The 3' boundary is likely confined to the region between non-coding exon 1 and non-coding exon 2. A genomic deletion involving the promoter (non-coding exon 1) region has been reported to segregate with BMPR1A-related disease in a single family (PMID: 20843829). A similar deletion involving the promoter region has also been reported an individual with congenital heart defect who was pending for juvenile polyposis (JP) screening (PMID: 22067610). Experimental studies have shown that deletion of this promoter region impairs the transcription of a reporter gene in vitro, and protein samples derived from individuals carrying this variant showed reduced BMPR1A protein levels compared to a control sample (PMID: 20843829). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
| Invitae | RCV001378404 | SCV001575961 | uncertain significance | Juvenile polyposis syndrome | 2022-08-20 | criteria provided, single submitter | clinical testing | This variant is a gross deletion that occurs in a non-coding region of the BMPR1A gene. It does not change the encoded amino acid sequence of the BMPR1A protein. This variant has not been reported in the literature in individuals affected with BMPR1A-related conditions. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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. |