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.1151C>T (p.Ala384Val)

CA350341728

425882 (ClinVar)

Gene: BMPR2
Condition: pulmonary arterial hypertension
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: f2b50603-89e4-4ca8-a22e-89d70ef18705
Approved on: 2025-01-03
Published on: 2025-01-03

HGVS expressions

NM_001204.7:c.1151C>T
NM_001204.7(BMPR2):c.1151C>T (p.Ala384Val)
NC_000002.12:g.202532607C>T
CM000664.2:g.202532607C>T
NC_000002.11:g.203397330C>T
CM000664.1:g.203397330C>T
NC_000002.10:g.203105575C>T
NG_009363.1:g.161281C>T
ENST00000374580.10:c.1151C>T
ENST00000638587.1:c.1082C>T
ENST00000374574.2:c.1151C>T
ENST00000374580.8:c.1151C>T
NM_001204.6:c.1151C>T
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Uncertain Significance

Met criteria codes 4
PP3 PM1 PM2_Supporting PS4_Supporting
Not Met criteria codes 5
PS1 PM5 BS1 BP4 BA1

Evidence Links 0

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 c.1151C>T (p.Ala384Val) variant is a missense variant located in exon 9 of the BMPR2 gene, predicted to cause substitution of alanine to valine encoding the functionally relevant catalytic kinase domain but without functional evidence indicating critical or non-critical (PM1_moderate). This variant is absent from gnomAD v2.1.1 (controls) and v4.1 (PM2_supporting). The REVEL prediction algorithm score is 0.917, AlphaMissense is 0.9915 indicating pathogenicity (PP3_met). The variant has been reported in one Japanese individual (PMID: 23675998) and one Chinese individual (PMID: 30578397, PMID: 32634488) with idiopathic PAH (PS4_supporting). PS2 was not assessed due to lack of paternity data. Functional studies have not been conducted for this variant (PS3 not assessed). In summary, this variant meets the criteria to be classified as a variant of uncertain significance for pulmonary arterial hypertension based on the ACMG/AMP criteria applied, as specified by the ClinGen Pulmonary Hypertension VCEP: PM1_moderate, PM2_supporting, PP3_supporting (VCEP specification version 1.1.0, 1/18/2024).
Met criteria codes
PP3
The REVEL prediction algorithm score is 0.917, AlphaMissense is 0.9915 indicating pathogenicity.
PM1
Variant is located in the conserved catalytic kinase domain but without functional evidence indicating critical or non-critical amino acid residue.
PM2_Supporting
Variant is absent from gnomAD v2.1.1 controls and v4.1.
PS4_Supporting
The variant has been reported in one Japanese individual (PMID: 23675998) and one Chinese individual (PMID: 30578397, PMID: 32634488) with idiopathic PAH.
Not Met criteria codes
PS1
The same amino acid change has not been reported.
PM5
No other variants at the amino acid residue have been reported.
BS1
Variant is absent from gnomAD v2.1.1 controls and v4.1.
BP4
The REVEL prediction algorithm score is 0.917, AlphaMissense is 0.9915 indicating pathogenicity.
BA1
Variant is absent from gnomAD v2.1.1 controls and v4.1.
Curation History
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