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]
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Variant: NM_001204.7(BMPR2):c.-924A>G

CA539000938

897238 (ClinVar)

Gene: BMPR2
Condition: pulmonary arterial hypertension
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 99cb166a-90f5-41cc-a1f4-12ebb9cb653c
Approved on: 2024-05-03
Published on: 2024-05-03

HGVS expressions

NM_001204.7:c.-924A>G
NM_001204.7(BMPR2):c.-924A>G
NC_000002.12:g.202376551A>G
CM000664.2:g.202376551A>G
NC_000002.11:g.203241274A>G
CM000664.1:g.203241274A>G
NC_000002.10:g.202949519A>G
NG_009363.1:g.5225A>G
ENST00000374580.10:c.-924A>G
NM_001204.6:c.-924A>G

Benign

Met criteria codes 3
BP4 BA1 BS2_Supporting
Not Met criteria codes 2
BP1 PP3

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 BMPR2 NM_001247.7 c.-924A>G variant is a 5' UTR variant with ClinVar variation ID: 897238 and allele ID: 883358. The highest population minor allele frequency in gnomAD v3.1.2 controls is 1.45% (115/7926 alleles, including 2 homozygotes) in the African/African American population, which is higher than the ClinGen Pulmonary Hypertension VCEP threshold of >1% for BA1, and therefore meets this stand-alone criterion (BA1). BS2_supporting was met based on the 2 observed homozygotes among gnomAD controls. BP4 was met based on the computational predictor, CADD, giving a score of 9.47 which is below the PH VCEP threshold of <=10.0. In summary, the variant meets the criteria to be classified as benign for pulmonary arterial hypertension based on ACMG/AMP criteria applied, as specified by the ClinGen Pulmonary Hypertension VCEP: BA1, BS2_supporting, BP4 (VCEP specification version 1.1, 1/18/2024).
Met criteria codes
BP4
BP4 was met based on the CADD score of 9.47 which is less than the threshold of <=10.
BA1
The highest population minor allele frequency in gnomAD v3.1.2 controls/biobanks is 0.1451 (115/7926) in African American population which is higher than the ClinGen Pulmonary Hypertension VCEP threshold of (>0.01) for BA1, and therefore meets this stand-alone criterion. Since it is a non-coding variant only gnomAD v3 and above was evaluated.
BS2_Supporting
This variant was present in 2 homozygotes in the African American population in gnomAD v3.1.2 controls/biobanks.
Not Met criteria codes
BP1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
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