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]

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Variant: NM_001204.7(BMPR2):c.1413+1G>A

CA350343048

425938 (ClinVar)

Gene: BMPR2

Condition: pulmonary arterial hypertension

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 9249a6a6-e582-4188-8103-6c06aaefa5a1

HGVS expressions

NM_001204.7:c.1413+1G>A

NM_001204.7(BMPR2):c.1413+1G>A

NC_000002.12:g.202542448G>A

CM000664.2:g.202542448G>A

NC_000002.11:g.203407171G>A

CM000664.1:g.203407171G>A

NC_000002.10:g.203115416G>A

NG_009363.1:g.171122G>A

ENST00000374580.10:c.1413+1G>A

ENST00000638587.1:c.1344+1G>A

ENST00000374574.2:c.1413+1G>A

ENST00000374580.8:c.1413+1G>A

NM_001204.6:c.1413+1G>A

Pathogenic

PS4_Moderate PVS1 PM2

BA1 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 1.1.0

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Pulmonary Hypertension VCEP

The NM_001204.7(BMPR2) c.1413+1G>A variant is located in the canonical donor splice site of intron 11, predicted to cause out-of-frame exon skipping and nonsense mediated decay (PVS1). The variant is absent from gnomAD v2.1.1 and v4.1 (PM2_supporting). The variant has been identified in 4 unrelated probands with pulmonary arterial hypertension (3 reported in ClinVar and 1 from a PH VCEP internal database). No segregation data or mode of inheritance information were available (BS4, PP1, PM6, PS2 not evaluated). In summary, this variant meets the criteria to be classified as pathogenic for autosomal dominant pulmonary arterial hypertension based on the ACMG/AMP criteria applied, as specified by the ClinGen Pulmonary Hypertension VCEP: PVS1, PM2_supporting, PS4_supporting. (VCEP specifications version 1.1, 1/18/2024)

PS4_Moderate

identified in >3 (n = 4) unrelated probands with pulmonary arterial hypertension (3 in CllinVar and 1 from internal PH VCEP database)

PVS1

canonical +1 splice site variant

PM2

absent from gnomAD

BA1

absent from gnomAD

BS1

absent from gnomAD

Approved on: 2024-05-07

Published on: 2024-05-07

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