Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Clingen Pulmonary Hypertension Variant Curation Expert Panel, |
RCV004549761 | SCV005043298 | likely benign | Pulmonary arterial hypertension | 2024-05-03 | reviewed by expert panel | curation | The NM_001204.7(BMPR2):c.2948G>A variant is a missense variant predicted to cause substitution of arginine to glutamine at amino acid position 983 (p.Arg983Gln). The highest population minor allele frequency in gnomAD v2.1.1 controls is 0.0034 (8/2358) in the Ashkenazi Jew population, which is higher than the ClinGen PH VCEP threshold (>0.1%) for BS1, and therefore meets this criterion (BS1). The computational predictor REVEL gives a score of 0.4, which is neither above nor below the thresholds predicting a damaging or benign impact on BMPR2 function. In summary, this variant meets the criteria to be classified as likely benign for pulmonary arterial hypertension based on the ACMG/AMP criteria applied, as specified by the ClinGen Pulmonary Hypertension VCEP: BS1. (VCEP specifications version 1.1, 1/18/2024) |
| Illumina Laboratory Services, |
RCV000373321 | SCV000426400 | benign | Pulmonary hypertension, primary, 1 | 2018-01-13 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. |
| Labcorp Genetics |
RCV001420986 | SCV000754708 | likely benign | Primary pulmonary hypertension | 2023-12-29 | criteria provided, single submitter | clinical testing | |
| ARUP Laboratories, |
RCV001812873 | SCV001156650 | uncertain significance | not provided | 2020-03-26 | criteria provided, single submitter | clinical testing | The BMPR2 c.2948G>A; p.Arg983Gln variant (rs148099152) is reported in ClinVar (Variation ID: 333652), and in the literature in an individual of Ashkenazi Jewish descent affected with pulmonary arterial hypertension (Newman 2004). However, this variant is found in the Ashkenazi Jewish population with an allele frequency of 0.46% (48/10366 alleles) in the Genome Aggregation Database, suggesting that it may be a polymorphism in this population. The arginine at codon 983 is highly conserved, and computational analyses (SIFT: damaging, PolyPhen-2: benign) predict conflicting effects of this variant on protein structure/function. Due to limited information, the clinical significance of the p.Arg983Gln variant is uncertain at this time. References: Newman JH et al. Genetic basis of pulmonary arterial hypertension: current understanding and future directions. J Am Coll Cardiol. 2004 Jun 16;43(12 Suppl S):33S-39S. |
| Centre for Mendelian Genomics, |
RCV000373321 | SCV001370451 | uncertain significance | Pulmonary hypertension, primary, 1 | 2016-01-01 | criteria provided, single submitter | clinical testing | This variant was classified as: Uncertain significance. |
| Centre for Mendelian Genomics, |
RCV000414928 | SCV000492681 | uncertain significance | Pulmonary arterial hypertension; Mitral valve prolapse; Right ventricular hypertrophy; Pulmonary artery dilatation; Right ventricular dilatation; Elevated right atrial pressure; Increased pulmonary vascular resistance; Right bundle branch block | 2016-01-13 | no assertion criteria provided | clinical testing |