Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000493580 | SCV000582375 | pathogenic | not provided | 2015-09-01 | criteria provided, single submitter | clinical testing | Although the c.1097delC deletion in the BMPR2 gene has not been reported to our knowledge, this variant causes a shift in reading frame starting at codon Proline 366, changing it to a Glutamine, and creating a premature stop codon at position 9 of the new reading frame, denoted p.Pro366GlnfsX9. This deletion is expected to result in either an abnormal, truncated protein product or loss of protein from this allele through nonsense-mediated mRNA decay. Other frameshift variants in the BMPR2 gene have been reported in HGMD in association with PAH (Stenson et al., 2014). Furthermore, the c.1097delC deletion was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations.In summary, c.1097delC in the BMPR2 gene is interpreted as a pathogenic variant. |
Labcorp Genetics |
RCV001386886 | SCV001587284 | pathogenic | Primary pulmonary hypertension | 2020-03-09 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in BMPR2 are known to be pathogenic (PMID: 16429395). This variant has been observed in individual(s) with pulmonary arterial hypertension (PMID: 19555857). This variant is also known as c.1095delC, p.R365fsX8 in the literature. ClinVar contains an entry for this variant (Variation ID: 425871). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Pro366Glnfs*9) in the BMPR2 gene. It is expected to result in an absent or disrupted protein product. |
Rare Disease Genomics Group, |
RCV000488847 | SCV000576163 | pathogenic | Pulmonary hypertension, primary, 1 | no assertion criteria provided | literature only |