2-202552837-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate
The NM_001204.7(BMPR2):c.1535A>G(p.Lys512Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_001204.7 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
BMPR2 | ENST00000374580.10 | c.1535A>G | p.Lys512Arg | missense_variant | Exon 11 of 13 | 1 | NM_001204.7 | ENSP00000363708.4 | ||
BMPR2 | ENST00000374574.2 | c.1535A>G | p.Lys512Arg | missense_variant | Exon 11 of 12 | 2 | ENSP00000363702.2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 33
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not provided Uncertain:1
The BMPR2 c.1535A>G; p.Lys512Arg variant, to our knowledge, is not reported in the medical literature or gene-specific databases. The variant is also absent from general population databases (Exome Variant Server, Genome Aggregation Database), indicating it is not a common polymorphism. However, another variant in the same codon, p.Lys512Thr, is reported in one family with pulmonary arterial hypertension and transfected expressed protein mislocalizes in cells (John 2015, Machado 2001). The lysine at codon 512 is highly conserved, but computational analyses (SIFT, PolyPhen-2) predict that this variant is tolerated. Due to limited information, the clinical significance of the p.Lys512Arg variant is uncertain at this time. References: John A et al. Defective cellular trafficking of the bone morphogenetic protein receptor type II by mutations underlying familial pulmonary arterial hypertension. Gene. 2015 Apr 25;561(1):148-56. Machado RD et al. BMPR2 haploinsufficiency as the inherited molecular mechanism for primary pulmonary hypertension. Am J Hum Genet. 2001 Jan;68(1):92-102. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at