2-202464911-G-T
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PM1PM2PM5PP2PP3_Strong
The NM_001204.7(BMPR2):c.179G>T(p.Cys60Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C60G) has been classified as Pathogenic.
Frequency
Consequence
NM_001204.7 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 11 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BMPR2 | NM_001204.7 | c.179G>T | p.Cys60Phe | missense_variant | 2/13 | ENST00000374580.10 | |
BMPR2 | XM_011511687.2 | c.179G>T | p.Cys60Phe | missense_variant | 2/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BMPR2 | ENST00000374580.10 | c.179G>T | p.Cys60Phe | missense_variant | 2/13 | 1 | NM_001204.7 | P1 | |
BMPR2 | ENST00000374574.2 | c.179G>T | p.Cys60Phe | missense_variant | 2/12 | 2 | |||
BMPR2 | ENST00000479069.1 | n.86G>T | non_coding_transcript_exon_variant | 1/3 | 3 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome Cov.: 31
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Pulmonary hypertension, primary, 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Apr 11, 2019 | This sequence change replaces cysteine with phenylalanine at codon 60 of the BMPR2 protein (p.Cys60Phe). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and phenylalanine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with BMPR2-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant disrupts the p.Cys60 amino acid residue in BMPR2. Other variant(s) that disrupt this residue have been observed in individuals with BMPR2-related conditions (PMID: 29743074, 11015450, 21737554, 26387786), which suggests that this may be a clinically significant amino acid residue. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at