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]
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • No CSPEC computer assertion could be determined for this classification!

Variant: NM_001204.7(BMPR2):c.2948G>A (p.Arg983Gln)

CA2061617

333652 (ClinVar)

Gene: BMPR2
Condition: pulmonary arterial hypertension
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 45d8759d-7438-4066-a6cc-7193f6524fdb
Approved on: 2024-05-03
Published on: 2024-05-03

HGVS expressions

NM_001204.7:c.2948G>A
NM_001204.7(BMPR2):c.2948G>A (p.Arg983Gln)
NC_000002.12:g.202559777G>A
CM000664.2:g.202559777G>A
NC_000002.11:g.203424500G>A
CM000664.1:g.203424500G>A
NC_000002.10:g.203132745G>A
NG_009363.1:g.188451G>A
ENST00000374580.10:c.2948G>A
ENST00000638587.1:c.2879G>A
ENST00000374574.2:c.*75G>A
ENST00000374580.8:c.2948G>A
NM_001204.6:c.2948G>A
More

Likely Benign

Met criteria codes 1
BS1
Not Met criteria codes 8
PM2 PM5 PM1 PS1 BA1 PP3 BS2 BP4

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 NM_001204.7(BMPR2):c.2948G>A variant is a missense variant predicted to cause substitution of arginine to glutamine at amino acid position 983 (p.Arg983Gln). The highest population minor allele frequency in gnomAD v2.1.1 controls is 0.0034 (8/2358) in the Ashkenazi Jew population, which is higher than the ClinGen PH VCEP threshold (>0.1%) for BS1, and therefore meets this criterion (BS1). The computational predictor REVEL gives a score of 0.4, which is neither above nor below the thresholds predicting a damaging or benign impact on BMPR2 function. In summary, this variant meets the criteria to be classified as likely benign for pulmonary arterial hypertension based on the ACMG/AMP criteria applied, as specified by the ClinGen Pulmonary Hypertension VCEP: BS1. (VCEP specifications version 1.1, 1/18/2024)
Met criteria codes
BS1
GnomAD v2.1.1 control population was evaluated. Allele frequency in Ashkenazi Jews control population is 0.3% (8/2358). The frequency is greater than 0.1% cutoff for BS1 for PAH.
Not Met criteria codes
PM2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM5
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
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.
PS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BA1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP3
The computational predictor REVEL gives a score of 0.4, which is neither above nor below the thresholds predicting a damaging or benign impact on BMPR2 function.
BS2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP4
The computational predictor REVEL gives a score of 0.4, which is neither above nor below the thresholds predicting a damaging or benign impact on BMPR2 function. SpliceAI does not predict an effect on splicing.
Curation History
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