Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000708244 | SCV000837354 | likely pathogenic | Generalized juvenile polyposis/juvenile polyposis coli | 2019-03-07 | 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 | RCV001378406 | SCV001575963 | likely pathogenic | Juvenile polyposis syndrome | 2021-08-16 | criteria provided, single submitter | clinical testing | This variant occurs in a non-coding region of the BMPR1A gene. It does not change the encoded amino acid sequence of the BMPR1A protein. A similar copy number variant has been observed in individual(s) with clinical features of BMPR1A-related conditions (PMID: 20843829, 22067610). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. Experimental studies have shown that a similar copy number variant affects BMPR1A function (PMID: 20843829). The region of the BMPR1A gene that includes the promoter/non-coding exon 1 has been determined to be clinically significant (PMID: 20843829, 21872883). Therefore, deletions that encompass that region are likely to be disease-causing. 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. |