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.2352C>T (p.Val784=)

CA2061522

333647 (ClinVar)

Gene: BMPR2 (HGNC:659)

Condition: pulmonary arterial hypertension (MONDO:0015924)

Inheritance Mode: Autosomal dominant inheritance

UUID: 56885255-cd86-4c5d-887f-dfd7f2b7ad29

Approved on: 2026-04-10

Published on: 2026-04-10

HGVS expressions

NM_001204.7:c.2352C>T

NM_001204.7(BMPR2):c.2352C>T (p.Val784=)

NC_000002.12:g.202556017C>T

CM000664.2:g.202556017C>T

NC_000002.11:g.203420740C>T

CM000664.1:g.203420740C>T

NC_000002.10:g.203128985C>T

NG_009363.1:g.184691C>T

ENST00000374580.10:c.2352C>T

ENST00000638587.1:c.2283C>T

ENST00000374574.2:c.1586+3129C>T

ENST00000374580.8:c.2352C>T

NM_001204.6:c.2352C>T

Uncertain Significance

PM2_Supporting BP7 BP4

PS4 BA1 PM1 BS1

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 2.0.0

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Pulmonary Hypertension VCEP

The NM_001204.7(BMPR2) c.2352C>T variant is a synonymous (silent) variant (p.Val784=). This variant is present in gnomADv2.1.1 controls at a frequency of 0.00002 and gnomADv4.1 at 0.00006 (PM2_supporting). In silico prediction algorithms indicate that the nucleotide is not highly conserved (REVEL score not available; CADD = 1.4; phyloP = 0.207) (BP4) and has no impact on splicing (SpliceAI = 0) (BP7). In summary, this variant is 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: BP4, BP7, PM2_supporting. (VCEP specifications version 2.0, 1/30/2026)

PM2_Supporting

Maximum allele frequency is 0.00002 in gnomAD v2.1.1 controls and 0.00006 in gnomAD v4.1.

BP7

BP4 is met and the SpliceAI score (0) predicts no impact on splicing.

BP4

REVEL score not available. CADD = 1.4 is below the PH VCEP established threshold for benignity of <= 10.

PS4

Very low allele frequency and not reported in the literature.

BA1

Variant has less than 5% allele frequency.

PM1

No functional domain using UniProt and NextProt.

BS1

Allele frequency is not greater due to disorder.

Curation History

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.