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.1277-9A>C

Curation Version - 1.1
Curation History
JSON LD for Version 1.1

CA645293837

425916 (ClinVar)

Gene: BMPR2

Condition: pulmonary arterial hypertension

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 04b0fbbd-af8b-472b-9e4f-124cf9f7bbe3

Approved on: 2025-10-03

Published on: 2025-10-03

HGVS expressions

NM_001204.7:c.1277-9A>C

NM_001204.7(BMPR2):c.1277-9A>C

NC_000002.12:g.202542302A>C

CM000664.2:g.202542302A>C

NC_000002.11:g.203407025A>C

CM000664.1:g.203407025A>C

NC_000002.10:g.203115270A>C

NG_009363.1:g.170976A>C

ENST00000374580.10:c.1277-9A>C

ENST00000638587.1:c.1208-9A>C

ENST00000374574.2:c.1277-9A>C

ENST00000374580.8:c.1277-9A>C

NM_001204.6:c.1277-9A>C

Uncertain Significance

BP4 PM2_Supporting PS1

BA1 BS1 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.1277-9A>C variant is a non-canonical splice site (-9) variant located in intron 9. The variant is absent from gnomAD v.2.1.1 and v4.1.0 (PM2_supporting) and was reported in a single proband with PAH (PMID: 19555857). In silico prediction (SpliceAI) indicates no impact on splicing (BP4). However, the variant is located in the same splice region as previously established pathogenic variants, NM_001204.7(BMPR2) c.1277-8A>G and c.1277-9A>G, classified by the PH VCEP (PS1). No familial segregation data were available, and no functional analysis has been reported for this variant. In summary, the 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: PS1, PM2_supporting, BP4 (VCEP specification version v1.1, 1/18/2024).

BP4

SpliceAI predicts no impact on acceptor or donor sites (score = 0)

PM2_Supporting

Variant is absent from controls (gnomAD v2.1.1 and v4.1.0)

PS1

Non-canonical splice variant located in the same splice region as previously established pathogenic variants, NM_001204.7(BMPR2) c.1277-8A>G and c.1277-9A>G, classified by the PH VCEP.

BA1

Variant is not present in gnomAD v2.1.1 and v4.1.0

BS1

Variant is not present in gnomAD v2.1.1 and v4.1.0

PP3

SpliceAI predicts no impact on splicing

Curation History

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