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 computer 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
UUID: 370663a6-33e3-49fb-b66f-293d99e1c5c7

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

Likely Benign

Met criteria codes 2
PP3 BS3
Not Met criteria codes 4
PS1 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 1.1.0

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. Therefore, this variant does not meet either of these population criteria. The REVEL computational prediction analysis tool produced a score of 0.8069, which is above the threshold (>0.75) for pathogenicity (PP3). Luciferase assay data indicated that variant transcriptional activity was comparable to wild-type, indicating no deleterious effect (BS3; PMID: 18321866). The PH Expert Panel reviewed the conflicting evidence (PP3) and felt it did not override the Likely Benign classification in this case. 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: BS3, PP3. (VCEP specifications version 1.1, 1/18/2024)
Met criteria codes
PP3
REVEL score: 0.8069
BS3
Cells transfected with the p.G182D variant have no damaging effect on transcriptional activity by luciferase assay (PMID: 18321866)

Not Met criteria codes
PS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM2
Allele frequency in the European population (gnomAD v2.1.1 controls) is greater than 0.01% (MAF: 15/42768 = 0.0003507)
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
Approved on: 2024-05-03
Published on: 2024-05-03
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