Evidence Repository
The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • No CSPEC computed assertion could be determined for this classification!

Variant: NM_001204.7(BMPR2):c.545G>A (p.Gly182Asp)

CA119936

8813 (ClinVar)

Gene: BMPR2
Condition: pulmonary arterial hypertension
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 370663a6-33e3-49fb-b66f-293d99e1c5c7
Approved on: 2026-01-30
Published on: 2026-01-31

HGVS expressions

NM_001204.7:c.545G>A
NM_001204.7(BMPR2):c.545G>A (p.Gly182Asp)
NC_000002.12:g.202514903G>A
CM000664.2:g.202514903G>A
NC_000002.11:g.203379626G>A
CM000664.1:g.203379626G>A
NC_000002.10:g.203087871G>A
NG_009363.1:g.143577G>A
ENST00000374580.10:c.545G>A
ENST00000638587.1:c.476G>A
ENST00000374574.2:c.545G>A
ENST00000374580.8:c.545G>A
NM_001204.6:c.545G>A
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Uncertain Significance

Met criteria codes 1
BS3
Not Met criteria codes 5
PS1 PP3 PM2 PM5 BS1

Evidence Links 1

Expert Panel

Criteria Specification Information

Criteria Specification: ClinGen Pulmonary Hypertension Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for BMPR2 Version 2.0.0

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
Pulmonary Hypertension VCEP
The NM_0001204.7(BMPR2) c.545G>A variant is a missense variant predicted to cause substitution of glycine by aspartic acid at amino acid 182 (p.Gly182Asp). The highest subpopulation minor allele frequency in gnomAD v2.1.1 (controls) is 0.0003507 in the European (non-Finnish) population, which is higher than the ClinGen PH VCEP threshold (<0.01%) for PM2 but lower than the threshold (>0.1%) for BS1. A similar AF in gnomAD v4.1 (non-Finnish Europeans, 388/1179912) confirms the non-application of PM2 (PM2 not met). Computational prediction tool scores (REVEL 0.8069, AlphaMissense 0.4252, CADD 16.92) did not yield two out of three of these above the PH VCEP thresholds (PP3 not met). Luciferase assay data indicated that variant transcriptional activity was comparable to wild-type, indicating no deleterious effect (BS3; PMID: 18321866). 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: no criteria scored. (VCEP specifications version 2.0, 1/30/2026)
Met criteria codes
BS3
Cells transfected with the p.G182D variant have no damaging effect on transcriptional activity by luciferase assay (PMID: 18321866)
Transcriptional activity of the p.G182D variant is comparable to wild-type using a luciferase assay PubMed:18321866
Not Met criteria codes
PS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP3
Computational prediction tool scores (REVEL 0.8069, AlphaMissense 0.4252, CADD 16.92) did not yield two out of three of these above the PH VCEP thresholds.
PM2
Allele frequency in the European population (gnomAD v2.1.1 controls) is greater than 0.01% (MAF: 15/42768 = 0.0003507). A similar AF in gnomAD v4.1 (non-Finnish Europeans, 388/1179912) confirms the non-application of PM2..
PM5
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS1
Allele frequency is less than 0.1% in gnomAD v2.1.1 controls
Curation History
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