2-202532582-C-G
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP5_Moderate
The NM_001204.7(BMPR2):c.1129-3C>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,452 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Consequence
NM_001204.7 splice_region, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
BMPR2 | ENST00000374580.10 | c.1129-3C>G | splice_region_variant, intron_variant | 1 | NM_001204.7 | ENSP00000363708.4 | ||||
BMPR2 | ENST00000374574.2 | c.1129-3C>G | splice_region_variant, intron_variant | 2 | ENSP00000363702.2 |
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251338Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135840
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461452Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727022
GnomAD4 genome Cov.: 31
ClinVar
Submissions by phenotype
Primary pulmonary hypertension Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Sep 27, 2024 | This sequence change falls in intron 8 of the BMPR2 gene. It does not directly change the encoded amino acid sequence of the BMPR2 protein. RNA analysis indicates that this variant induces altered splicing and may result in an absent or altered protein product. This variant is present in population databases (no rsID available, gnomAD 0.01%). This variant has been observed in individuals with pulmonary hypertension (PMID: 11115378, 16717148, 19206171, 21737554). ClinVar contains an entry for this variant (Variation ID: 425878). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that this variant results in skipping of exon 9, and produces a non-functional protein and/or introduces a premature termination codon (PMID: 19206171). For these reasons, this variant has been classified as Pathogenic. - |
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