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]

Link to SEPIO compliant JSON-LD document

Variant: NM_001204.7(BMPR2):c.2352C>T (p.Val784=)

CA2061522

333647 (ClinVar)

Gene: BMPR2

Condition: pulmonary arterial hypertension

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 56885255-cd86-4c5d-887f-dfd7f2b7ad29

Approved on: 2024-05-03

Published on: 2024-05-03

HGVS expressions

NM_001204.7:c.2352C>T

NM_001204.7(BMPR2):c.2352C>T (p.Val784=)

NC_000002.12:g.202556017C>T

CM000664.2:g.202556017C>T

NC_000002.11:g.203420740C>T

CM000664.1:g.203420740C>T

NC_000002.10:g.203128985C>T

NG_009363.1:g.184691C>T

ENST00000374580.10:c.2352C>T

ENST00000638587.1:c.2283C>T

ENST00000374574.2:c.1586+3129C>T

ENST00000374580.8:c.2352C>T

NM_001204.6:c.2352C>T

Uncertain Significance

BP7 PM2_Supporting

PS4 PM1 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.2352C>T variant is a synonymous (silent) variant (p.Val784=). This variant is present in gnomAD v2.1.1 controls at a frequency of 0.00002 (PM2_supporting). It is not predicted by SpliceAI to impact splicing. In addition, it occurs at a nucleotide that is not conserved as shown by phyloP = 0.207 (BP7). In summary, this variant is 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: BP7, PM2_supporting. (VCEP specifications version 1.1, 1/18/2024)

BP7

Located in middle of exon 12 and the nucleotide is not highly conserved. SpliceAI predicts no impact on splicing.

PM2_Supporting

Maximum allele frequency is 0.00002.

PS4

Very low allele frequency and not reported in the literature.

PM1

No functional domain using UniProt and NextProt.

BA1

Variant has less than 5% allele frequency.

BS1

Allele frequency is not greater due to disorder.

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