Variant: NM_001204.7(BMPR2):c.1087C>G (p.Leu363Val)

CA2061285

1309924 (ClinVar)

Gene: BMPR2

Condition: pulmonary arterial hypertension

Inheritance Mode: Autosomal dominant inheritance

UUID: af39a3f7-9f0a-4422-befe-2a231862a790

Approved on: 2024-04-30

Published on: 2024-04-30

HGVS expressions

NM_001204.7:c.1087C>G
NM_001204.7(BMPR2):c.1087C>G (p.Leu363Val)
NC_000002.12:g.202530913C>G
CM000664.2:g.202530913C>G
NC_000002.11:g.203395636C>G
CM000664.1:g.203395636C>G
NC_000002.10:g.203103881C>G
NG_009363.1:g.159587C>G
ENST00000374580.10:c.1087C>G
ENST00000638587.1:c.1018C>G
ENST00000374574.2:c.1087C>G
ENST00000374580.8:c.1087C>G
NM_001204.6:c.1087C>G

Uncertain Significance

• Met criteria codes: BP4 PM1 PM2

• Not Met criteria codes: BA1 BS1 BS2 PP3 PS4

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

Evidence submitted by expert panel

Pulmonary Hypertension VCEP

The BMPR2 c.1087C>G is a missense variant predicted to cause substitution of leucine to valine at amino acid position 363 ((p.(Leu363Val)). This variant is absent from gnomAD version2.1.1 controls and v3.1.2 (PM2_supporting met). The variant resides in the highly conserved protein kinase domain without functional evidence for a critical or non-critical role on protein function (PM1 met). The variant is predicted to have no effect on protein function with REVEL score of 0.24, which meets the threshold for BP4 (<0.25). There is another individual with the same variant in ClinVar but with insufficient evidence for a pulmonary arterial hypertension diagnosis. In summary, the variant meets the criteria to be classified as a variant of unknown significance (VUS) for pulmonary arterial hypertension based on the ACMG/AMP criteria applied, as specified by the ClinGen Pulmonary Hypertension VCEP: PM2_supporting, PM1, BP4 (VCEP specification version 1.1, 1/18/2024).

Met criteria codes

• BP4: REVEL score is 0.24
• PM1: Variant resides within the highly conserved protein kinase domain (aa.203-504). There is no functional data available specifying whether the residue is critical or not critical to protein function.
• PM2: Variant is absent from gnomAD v2.1.1 controls and v3.1.2

Not Met criteria codes

• BA1: Variant is absent from gnomAD v2.1.1 controls and v3.1.2
• BS1: Variant is absent from gnomAD v2.1.1 controls and v3.1.2
• BS2: Variant was not observed as a homozygous allele in gnomAD v2.1.1 controls.
• PP3: REVEL score is 0.24
• PS4: There is another individual with the same variant in ClinVar but with insufficient evidence for a pulmonary arterial hypertension diagnosis.