chr2-202376551-A-G
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_001204.7(BMPR2):c.-924A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00484 in 127,596 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★★).
Frequency
Genomes: 𝑓 0.0048 ( 2 hom., cov: 25)
Consequence
BMPR2
NM_001204.7 5_prime_UTR
NM_001204.7 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.0850
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.69).
BP6
?
Variant 2-202376551-A-G is Benign according to our data. Variant chr2-202376551-A-G is described in ClinVar as [Benign]. Clinvar id is 897238.Status of the report is reviewed_by_expert_panel, 3 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00484 (617/127596) while in subpopulation AFR AF= 0.0149 (534/35832). AF 95% confidence interval is 0.0139. There are 2 homozygotes in gnomad4. There are 294 alleles in male gnomad4 subpopulation. Median coverage is 25. This position pass quality control queck.
BS2
?
High AC in GnomAd at 616 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BMPR2 | NM_001204.7 | c.-924A>G | 5_prime_UTR_variant | 1/13 | ENST00000374580.10 | ||
BMPR2 | XM_011511687.2 | c.-924A>G | 5_prime_UTR_variant | 1/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BMPR2 | ENST00000374580.10 | c.-924A>G | 5_prime_UTR_variant | 1/13 | 1 | NM_001204.7 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00483 AC: 616AN: 127506Hom.: 2 Cov.: 25
GnomAD3 genomes
?
AF:
AC:
616
AN:
127506
Hom.:
Cov.:
25
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? AF: 0.00484 AC: 617AN: 127596Hom.: 2 Cov.: 25 AF XY: 0.00479 AC XY: 294AN XY: 61330
GnomAD4 genome
?
AF:
AC:
617
AN:
127596
Hom.:
Cov.:
25
AF XY:
AC XY:
294
AN XY:
61330
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
ClinVar
Significance: Benign
Submissions summary: Uncertain:1Benign:2
Revision: reviewed by expert panel
LINK: link
Submissions by phenotype
Pulmonary hypertension, primary, 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Pulmonary arterial hypertension Benign:1
Benign, reviewed by expert panel | curation | Clingen Pulmonary Hypertension Variant Curation Expert Panel, ClinGen | May 03, 2024 | The BMPR2 NM_001247.7 c.-924A>G variant is a 5' UTR variant with ClinVar variation ID: 897238 and allele ID: 883358. The highest population minor allele frequency in gnomAD v3.1.2 controls is 1.45% (115/7926 alleles, including 2 homozygotes) in the African/African American population, which is higher than the ClinGen Pulmonary Hypertension VCEP threshold of >1% for BA1, and therefore meets this stand-alone criterion (BA1). BS2_supporting was met based on the 2 observed homozygotes among gnomAD controls. BP4 was met based on the computational predictor, CADD, giving a score of 9.47 which is below the PH VCEP threshold of <=10.0. In summary, the variant meets the criteria to be classified as benign for pulmonary arterial hypertension based on ACMG/AMP criteria applied, as specified by the ClinGen Pulmonary Hypertension VCEP: BA1, BS2_supporting, BP4 (VCEP specification version 1.1, 1/18/2024). - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 07, 2018 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at