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]

Link to SEPIO compliant JSON-LD document

Variant: NM_001204.7(BMPR2):c.1766A>G (p.Tyr589Cys)

CA2061448

425966 (ClinVar)

Gene: BMPR2

Condition: pulmonary arterial hypertension

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 6a60247f-8518-4f06-8c9d-6a6d73623484

Approved on: 2024-05-03

Published on: 2024-05-03

HGVS expressions

NM_001204.7:c.1766A>G

NM_001204.7(BMPR2):c.1766A>G (p.Tyr589Cys)

NC_000002.12:g.202555431A>G

CM000664.2:g.202555431A>G

NC_000002.11:g.203420154A>G

CM000664.1:g.203420154A>G

NC_000002.10:g.203128399A>G

NG_009363.1:g.184105A>G

ENST00000374580.10:c.1766A>G

ENST00000638587.1:c.1697A>G

ENST00000374574.2:c.1586+2543A>G

ENST00000374580.8:c.1766A>G

NM_001204.6:c.1766A>G

Likely Benign

BS1

BP4 PM1 PM2 PP3

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.1766A>G variant is a missense variant predicted to result in a tyrosine to cysteine substitution at amino acid 589 (p.Tyr589Cys). The minor allele frequency in gnomAD v2.1.1 controls at a frequency of 0.001511 (22/14,556 alleles) which is above the cut-off of 0.1% for PAH (BS1 met). The variant is located outside of the critical extracellular and kinase domains of BMPR2 (PM1 not met). The REVEL score is 0.577, not exceeding the threshold of >=0.75 (PP3 not met) or <=0.25 (BP4 not met). No functional data was available and SpliceAI does not predict an effect on splicing. In summary, the 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: BS1 (VCEP specification version 1.1, 1/18/2024).

BS1

This variant is found in the Finnish population of gnomAD v2.1.1 controls at a frequency of 0.001511 (22/14,556 alleles) which is above the cut-off of 0.1% for PAH.

BP4

The REVEL score for this variant is 0.577 which is above the threshold of <=0.25 defined by the PH VCEP. SpliceAI does not predict an effect on splicing.

PM1

The amino acid change that results from this variant is outside of the critical extracellular and kinase domains.

PM2

This variant is found in the Finnish population of gnomAD v2.1.1 controls at a frequency of 0.001511 (22/14,556 alleles) which is above the cut-off of 0.01% for PAH.

PP3

The REVEL score for this variant is 0.577 which is below the threshold of >=0.75 defined by the PH VCEP and SpliceAI predicts no effect on splicing (score = 0).

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.