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]

Variant: NM_001204.7(BMPR2):c.1698T>A (p.Ile566=)

CA64042886

898486 (ClinVar)

Gene: BMPR2 (HGNC:659)

Condition: pulmonary arterial hypertension (MONDO:0015924)

Inheritance Mode: Autosomal dominant inheritance

UUID: 328d0d54-f6de-427b-a63c-08ed41237655

Approved on: 2024-05-03

Published on: 2024-05-03

HGVS expressions

NM_001204.7:c.1698T>A

NM_001204.7(BMPR2):c.1698T>A (p.Ile566=)

NC_000002.12:g.202555363T>A

CM000664.2:g.202555363T>A

NC_000002.11:g.203420086T>A

CM000664.1:g.203420086T>A

NC_000002.10:g.203128331T>A

NG_009363.1:g.184037T>A

ENST00000374580.10:c.1698T>A

ENST00000638587.1:c.1629T>A

ENST00000374574.2:c.1586+2475T>A

ENST00000374580.8:c.1698T>A

NM_001204.6:c.1698T>A

Uncertain Significance

PM2_Supporting BP7 BP4

BS1 BA1 PM1

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.1698T>A variant is a synonymous (silent) variant (p.Ile566=) that is not predicted by SpliceAI to impact splicing (BP4, BP7). This variant is absent from gnomAD v2.1.1 controls (PM2_supporting). Due to conflicting evidence, 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: BP4, BP7, PM2_supporting. (VCEP specifications version 1.1, 1/18/2024)

PM2_Supporting

Variant allele is absent from controls dataset (gnomAD v2.1.1)

BP7

SpliceAI predicts no impact on splicing and the nucleotide is not highly conserved

BP4

Low CADD score (no REVEL score available as variant is synonymous)

BS1

Allele frequency is less than 0.1% in controls (gnomAD v2.1.1)

BA1

Allele frequency is less than 1% in controls (gnomAD v2.1.1)

PM1

Located in a domain of undefined function

Curation History

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