rs1085307352
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_001204.7(BMPR2):c.1424C>A(p.Ser475Ter) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,756 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★★★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_001204.7 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BMPR2 | NM_001204.7 | c.1424C>A | p.Ser475Ter | stop_gained | 11/13 | ENST00000374580.10 | |
BMPR2 | XM_011511687.2 | c.1424C>A | p.Ser475Ter | stop_gained | 11/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BMPR2 | ENST00000374580.10 | c.1424C>A | p.Ser475Ter | stop_gained | 11/13 | 1 | NM_001204.7 | P1 | |
BMPR2 | ENST00000374574.2 | c.1424C>A | p.Ser475Ter | stop_gained | 11/12 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461756Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1AN XY: 727178
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Pulmonary arterial hypertension Pathogenic:2
Pathogenic, reviewed by expert panel | curation | Clingen Pulmonary Hypertension Variant Curation Expert Panel, ClinGen | May 03, 2024 | The BMPR2 c.1424C>A variant is a nonsense mutation in the kinase domain (exon 11 of 13). It is predicted to result in nonsense mediated mRNA decay, and therefore meets the criteria for PVS1. It is absent from gnomAD v2.1.1 (all samples), meeting PM2_supporting. There are three reports of this variant in the literature (PMIDs 16429395, 20534176 and 32581362). However, since PMID 16429395 summarized data from multiple countries, including the UK and French populations that were the subject of the later papers, it is not possible to determine if all three probands are independent. Thus conservatively, only counted 2 probands were counted (PS4_supporting). In summary, the variant meets the criteria to be classified as pathogenic for pulmonary arterial hypertension based on ACMG/AMP criteria applied, as specified by the ClinGen Pulmonary Hypertension VCEP: PVS1, PM2_supporting, PS4_supporting (VCEP specification version 1.1, 1/18/2024). - |
Pathogenic, no assertion criteria provided | research | NIHR Bioresource Rare Diseases, University of Cambridge | - | - - |
Pulmonary hypertension, primary, 1 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | Rare Disease Genomics Group, St George's University of London | - | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at