rs1061157
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_001204.7(BMPR2):c.2811G>A(p.Arg937=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.118 in 1,613,998 control chromosomes in the GnomAD database, including 12,623 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.093 ( 883 hom., cov: 32)
Exomes 𝑓: 0.12 ( 11740 hom. )
Consequence
BMPR2
NM_001204.7 synonymous
NM_001204.7 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.44
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 -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.55).
BP6
?
Variant 2-202556476-G-A is Benign according to our data. Variant chr2-202556476-G-A is described in ClinVar as [Benign]. Clinvar id is 136529.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-202556476-G-A is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=1.44 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.231 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BMPR2 | NM_001204.7 | c.2811G>A | p.Arg937= | synonymous_variant | 12/13 | ENST00000374580.10 | |
BMPR2 | XM_011511687.2 | c.2811G>A | p.Arg937= | synonymous_variant | 12/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BMPR2 | ENST00000374580.10 | c.2811G>A | p.Arg937= | synonymous_variant | 12/13 | 1 | NM_001204.7 | P1 | |
BMPR2 | ENST00000374574.2 | c.1587-3220G>A | intron_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0934 AC: 14207AN: 152100Hom.: 883 Cov.: 32
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GnomAD3 exomes AF: 0.119 AC: 29883AN: 251166Hom.: 2163 AF XY: 0.127 AC XY: 17251AN XY: 135762
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GnomAD4 exome AF: 0.120 AC: 175695AN: 1461780Hom.: 11740 Cov.: 33 AF XY: 0.124 AC XY: 90147AN XY: 727184
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GnomAD4 genome ? AF: 0.0933 AC: 14196AN: 152218Hom.: 883 Cov.: 32 AF XY: 0.0959 AC XY: 7138AN XY: 74420
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ClinVar
Significance: Benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:3
Benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 06, 2013 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Feb 21, 2013 | Arg937Arg in exon 12 of BMPR2: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue and is not located wit hin the splice consensus sequence. It has been identified in 12.6% (1085/8600) o f European American chromosomes from a broad population by the NHLBI Exome Seque ncing Project (http://evs.gs.washington.edu/EVS; dbSNP rs1061157). - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Nov 29, 2023 | - - |
Primary pulmonary hypertension Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Pulmonary hypertension, primary, 1 Benign:1
Benign, 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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
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Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at