ClinVar Miner

Submissions for variant NM_001204.7(BMPR2):c.2618G>A (p.Arg873Gln)

gnomAD frequency: 0.00007  dbSNP: rs201781338
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Clingen Pulmonary Hypertension Variant Curation Expert Panel, ClinGen RCV004551615 SCV005043302 benign Pulmonary arterial hypertension 2024-05-03 reviewed by expert panel curation The c.2618G>A variant (NM_001204.7) in BMPR2 is a missense variant predicted to cause substitution of arginine by glutamine at amino acid 873 (p.Arg873Gln). This variant has been reported not to segregate with pulmonary arterial hypertension in one affected family member from one family (BS4; Internal lab contributor). The highest population minor allele frequency in gnomAD v2.2.1 controls is 0.001595 in Other East Asian population, which is higher than the ClinGen Pulmonary Hypertension VCEP threshold (>=0.001) for BS1, and therefore meets this criterion (BS1). In vitro reporter system assay in mouse embryonic endothelial cells showed that the c.2618 G>A variant activate BRE-Luc (specific reporter gene for Smad1/5 activation) in response to BMP4 treatment in a similar way as the wild-type BMPR2 reporter gene. However the impairment of another function through an alternative signaling pathway of BMPRII could not be excluded (PMID 25429696)(BS3_Supporting). In summary, this variant meets the criteria to be classified as benign for pulmonary arterial hypertension based on the ACMG/AMP criteria applied, as specified by the ClinGen Pulmonary Hypertension VCEP (specification version 1.1, 1/18/2024): BS4, BS1, BS3_Supporting.
Labcorp Genetics (formerly Invitae), Labcorp RCV001391335 SCV001005565 likely benign Primary pulmonary hypertension 2023-12-22 criteria provided, single submitter clinical testing
Rare Disease Genomics Group, St George's University of London RCV000488657 SCV000576302 uncertain significance Pulmonary hypertension, primary, 1 no assertion criteria provided literature only
Center for Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong University RCV001662473 SCV001877126 likely pathogenic Genetic non-acquired premature ovarian failure 2019-10-01 no assertion criteria provided research

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