chr2-202513675-CT-C
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1
The NM_001204.7(BMPR2):c.419-38del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 1,470,308 control chromosomes in the GnomAD database, including 12,722 homozygotes. Variant has been reported in ClinVar as Benign (★★★).
Frequency
Genomes: 𝑓 0.13 ( 1266 hom., cov: 30)
Exomes 𝑓: 0.13 ( 11456 hom. )
Consequence
BMPR2
NM_001204.7 intron
NM_001204.7 intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 1.28
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 Benign. Variant got -16 ACMG points.
BP6
?
Variant 2-202513675-CT-C is Benign according to our data. Variant chr2-202513675-CT-C is described in ClinVar as [Benign]. Clinvar id is 548685.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr2-202513675-CT-C is described in Lovd as [Benign].
BA1
?
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.133 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BMPR2 | NM_001204.7 | c.419-38del | intron_variant | ENST00000374580.10 | |||
BMPR2 | XM_011511687.2 | c.419-38del | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BMPR2 | ENST00000374580.10 | c.419-38del | intron_variant | 1 | NM_001204.7 | P1 | |||
BMPR2 | ENST00000374574.2 | c.419-38del | intron_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.125 AC: 19016AN: 151826Hom.: 1262 Cov.: 30
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GnomAD3 exomes AF: 0.126 AC: 31203AN: 246956Hom.: 2207 AF XY: 0.126 AC XY: 16832AN XY: 133982
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GnomAD4 exome AF: 0.128 AC: 168474AN: 1318366Hom.: 11456 Cov.: 16 AF XY: 0.128 AC XY: 84715AN XY: 663834
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GnomAD4 genome ? AF: 0.125 AC: 19045AN: 151942Hom.: 1266 Cov.: 30 AF XY: 0.127 AC XY: 9412AN XY: 74272
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ClinVar
Significance: Benign
Submissions summary: Uncertain:1Benign:3
Revision: reviewed by expert panel
LINK: link
Submissions by phenotype
Pulmonary arterial hypertension associated with congenital heart disease Uncertain:1
Uncertain significance, criteria provided, single submitter | case-control | Wendy Chung Laboratory, Columbia University Medical Center | Jun 27, 2018 | - - |
Pulmonary arterial hypertension Benign:1
Benign, reviewed by expert panel | curation | Clingen Pulmonary Hypertension Variant Curation Expert Panel, ClinGen | May 03, 2024 | The BMPR2 c.419-38del is an intronic variant at Intron 3. The highest population minor allele frequency in gnomAD v2.1.1 (controls) is 0.1814 (2514/13856 alleles) in European (Finnish) population, which is higher than the ClinGen Pulmonary Hypertension Expert Panel threshold (>0.01) for BA1, and therefore meets this stand-alone criterion (BA1). This variant has been observed in 1160 times in homozygous state in healthy individuals (BS2). The computational splicing predictor SpliceAI gives a score of (0.00) for acceptor splice site loss suggesting that the variant has no impact on splicing (BP4). In summary, the variant is classified as benign for pulmonary arterial hypertension based on the ACMG/AMP criteria applied, as specified by the ClinGen Pulmonary Hypertension VCEP: BA1, BS2, BP4 (VCEP specification version v 1.1, 1/18/2024). - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 20, 2019 | This variant is associated with the following publications: (PMID: 30029678) - |
Primary pulmonary hypertension Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 15, 2024 | - - |
Computational scores
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at