Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000198060 | SCV000249646 | pathogenic | not provided | 2015-04-24 | criteria provided, single submitter | clinical testing | Although the c.186dupA pathogenic variant in the BMPR2 gene has not been reported to our knowledge, this variant causes a shift in reading frame starting at codon Glycine 63, changing it to an Arginine, and creating a premature stop codon at position 2 of the new reading frame, denoted p.Gly63ArgfsX2. This variant 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 P et al., 2014). Furthermore, the c.186dupA variant has not been observed in approximately 6,500 individuals of European and African American background in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. In summary, c.186dupA in the BMPR2 gene is interpreted as a pathogenic variant. |
Labcorp Genetics |
RCV001386215 | SCV001586354 | pathogenic | Primary pulmonary hypertension | 2023-04-28 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 212814). This variant has not been reported in the literature in individuals affected with BMPR2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gly63Argfs*2) in the BMPR2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BMPR2 are known to be pathogenic (PMID: 16429395). |
John Welsh Cardiovascular Diagnostic Laboratory, |
RCV002285150 | SCV002575054 | pathogenic | Pulmonary arterial hypertension | 2022-09-26 | no assertion criteria provided | clinical testing |