Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

Variant: NM_001204.7(BMPR2):c.86A>G (p.Asn29Ser)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA2061034

333638 (ClinVar)

Gene: BMPR2

Condition: pulmonary arterial hypertension

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: fbdadf39-ffbe-40f5-a79c-af267f12dcf5

Approved on: 2024-09-10

Published on: 2024-09-10

HGVS expressions

NM_001204.7:c.86A>G

NM_001204.7(BMPR2):c.86A>G (p.Asn29Ser)

NC_000002.12:g.202464818A>G

CM000664.2:g.202464818A>G

NC_000002.11:g.203329541A>G

CM000664.1:g.203329541A>G

NC_000002.10:g.203037786A>G

NG_009363.1:g.93492A>G

ENST00000374580.10:c.86A>G

ENST00000638587.1:c.11A>G

ENST00000374574.2:c.86A>G

ENST00000374580.8:c.86A>G

NM_001204.6:c.86A>G

Likely Benign

BS1

PP3 BP4

Evidence Links 0

Expert Panel

Pulmonary Hypertension VCEP

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 c.86A>G missense variant is predicted to cause a substitution of asparagine to serine at amino acid position 29 (p.Asn29Ser) in exon 2 within the signal peptide domain. The highest population minor allele frequency in gnomAD v2.1.1 controls is 0.006265 (v4.1.0 is 0.007668) in African/African American population, which is higher than the ClinGen Pulmonary Hypertension VECP threshold ≥0.1% for BS1, and therefore meets this criterion. The computational predictor REVEL gives a score of 0.497 indicating neither PP3 (≥0.75) nor BP4 (≤0.25) met. SpliceAI algorithm predicts no deleterious effect on acceptor or donor splice site. In summary, the variant meets the criteria to be classified as variant of likely benign for pulmonary arterial hypertension based on the ACMG/AMP criteria applied, as specified by the ClinGen Pulmonary Hypertension VCEP: BS1 (VCEP specification version 1.1, 1/18/2024).

BS1

The highest population minor allele frequency in gnomAD v2.1.1 controls is 0.006265 (v4.1.0 is 0.007668) in African/African American population, which is higher than the ClinGen Pulmonary Hypertension VECP threshold ≥0.1% for BS1, and therefore meets this criterion.

PP3

The computational predictor REVEL score for the variant is 0.276, which does not meet PP3 (≥0.75) nor BP4 (≤0.25).

BP4

The computational predictor REVEL gives a score of 0.497 indicating neither PP3 (≥0.75) nor BP4 (≤0.25) met. SpliceAI algorithm predicts no deleterious effect on acceptor or donor splice site.

Curation History

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