rs370120266
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP2PP5
The NM_001204.7(BMPR2):c.71C>A(p.Ala24Glu) variant causes a missense change. The variant allele was found at a frequency of 0.0000031 in 1,614,006 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000027 ( 0 hom. )
Consequence
BMPR2
NM_001204.7 missense
NM_001204.7 missense
Scores
5
14
Clinical Significance
Conservation
PhyloP100: 4.46
Genes affected
BMPR2 (HGNC:1078): (bone morphogenetic protein receptor type 2) This gene encodes a member of the bone morphogenetic protein (BMP) receptor family of transmembrane serine/threonine kinases. The ligands of this receptor are members of the TGF-beta superfamily. BMPs are involved in endochondral bone formation and embryogenesis. These proteins transduce their signals through the formation of heteromeric complexes of two different types of serine (threonine) kinase receptors: type I receptors of about 50-55 kD and type II receptors of about 70-80 kD. Mutations in this gene have been associated with primary pulmonary hypertension, both familial and fenfluramine-associated, and with pulmonary venoocclusive disease. [provided by RefSeq, May 2020]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant in gene, where missense usually causes diseases (based on misZ statistic), BMPR2. . Gene score misZ 2.0624 (greater than the threshold 3.09). Trascript score misZ 3.2701 (greater than threshold 3.09). GenCC has associacion of gene with pulmonary hypertension, primary, 1, congenital heart disease, heritable pulmonary arterial hypertension, pulmonary arterial hypertension.
PP5
Variant 2-202377545-C-A is Pathogenic according to our data. Variant chr2-202377545-C-A is described in ClinVar as [Pathogenic]. Clinvar id is 425687.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BMPR2 | NM_001204.7 | c.71C>A | p.Ala24Glu | missense_variant | 1/13 | ENST00000374580.10 | |
BMPR2 | XM_011511687.2 | c.71C>A | p.Ala24Glu | missense_variant | 1/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BMPR2 | ENST00000374580.10 | c.71C>A | p.Ala24Glu | missense_variant | 1/13 | 1 | NM_001204.7 | P1 | |
BMPR2 | ENST00000374574.2 | c.71C>A | p.Ala24Glu | missense_variant | 1/12 | 2 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152222Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000400 AC: 1AN: 250006Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135458
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GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461784Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 727200
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152222Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74360
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Uncertain
D;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T
M_CAP
Uncertain
D
MetaRNN
Uncertain
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;N
MutationTaster
Benign
N;N
PrimateAI
Benign
T
PROVEAN
Benign
N;N
REVEL
Uncertain
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
B;.
Vest4
MutPred
Gain of solvent accessibility (P = 0.0145);Gain of solvent accessibility (P = 0.0145);
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at