Evidence Repository
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.218C>G (p.Ser73Ter)

CA278072

8797 (ClinVar)

Gene: BMPR2
Condition: pulmonary arterial hypertension
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 3f3b87be-41dc-4c8f-a0ce-53b1877cfd32
Approved on: 2024-05-03
Published on: 2024-05-03

HGVS expressions

NM_001204.7:c.218C>G
NM_001204.7(BMPR2):c.218C>G (p.Ser73Ter)
NC_000002.12:g.202464950C>G
CM000664.2:g.202464950C>G
NC_000002.11:g.203329673C>G
CM000664.1:g.203329673C>G
NC_000002.10:g.203037918C>G
NG_009363.1:g.93624C>G
ENST00000374580.10:c.218C>G
ENST00000638587.1:c.143C>G
ENST00000374574.2:c.218C>G
ENST00000374580.8:c.218C>G
ENST00000479069.1:n.125C>G
NM_001204.6:c.218C>G

Pathogenic

Met criteria codes 3
PS4_Supporting PM2_Supporting PVS1
Not Met criteria codes 3
PM1 BA1 BS1

Evidence Links 0

Expert Panel

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 c.218C>G, (p.Ser73Ter) (NM_001204.7) variant in BMPR2 is a nonsense variant predicted to cause a premature stop codon in biologically-relevant-exon 2 leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1; PMID: 16429395). This variant has been reported in 2 pulmonary arterial hypertension probands (PS4_Supporting) (PMID: 26387786 ; PMID: 32581362). This variant is absent from gnomAD v2.1.1 controls (PM2_Supporting). In summary, this variant meets the criteria to be classified as pathogenic for pulmonary arterial hypertension based on the ACMG/AMP criteria applied, as specified by the ClinGen Pulmonary Hypertension VCEP (specification version 11, 1/18/2024): PVS1, PS4_Supporting, PM2_Supporting.
Met criteria codes
PS4_Supporting
This variant has been reported in 2 probands meeting pulmonary arterial hypertension (PS4_Supporting;PMID: 26387786 ; PMID: 32581362).
PM2_Supporting
This variant is absent from gnomAD v2.1.1 (PM2_Supporting).
PVS1
The c.218C>G, (p.Ser73Ter) (NM_001204.7) variant in BMPR2 is a nonsense variant predicted to cause a premature stop codon in biologically-relevant-exon 2 leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1; PMID: 16429395).
Not Met criteria codes
PM1
This variant does not reside within a region of BMPR2 that is defined as a mutational hotspot or critical functional domain by the ClinGen Pulmonary Hypertension VCEP.
BA1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
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