rs1555786156
Positions:
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1_StrongPM2PP5_Moderate
The NM_001200.4(BMP2):c.987C>A(p.Cys329Ter) variant causes a stop gained change involving the alteration of a non-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 Likely pathogenic (★).
Frequency
Genomes: not found (cov: 31)
Consequence
BMP2
NM_001200.4 stop_gained
NM_001200.4 stop_gained
Scores
2
4
1
Clinical Significance
Conservation
PhyloP100: 0.855
Genes affected
BMP2 (HGNC:1069): (bone morphogenetic protein 2) This gene encodes a secreted ligand of the TGF-beta (transforming growth factor-beta) superfamily of proteins. Ligands of this family bind various TGF-beta receptors leading to recruitment and activation of SMAD family transcription factors that regulate gene expression. The encoded preproprotein is proteolytically processed to generate each subunit of the disulfide-linked homodimer, which plays a role in bone and cartilage development. Duplication of a regulatory region downstream of this gene causes a form of brachydactyly characterized by a malformed index finger and second toe in human patients. [provided by RefSeq, Jul 2016]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
PVS1
?
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. There are 4 pathogenic variants in the truncated region.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 20-6778885-C-A is Pathogenic according to our data. Variant chr20-6778885-C-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 492937.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BMP2 | NM_001200.4 | c.987C>A | p.Cys329Ter | stop_gained | 3/3 | ENST00000378827.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BMP2 | ENST00000378827.5 | c.987C>A | p.Cys329Ter | stop_gained | 3/3 | 1 | NM_001200.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD3 genomes
?
Cov.:
31
GnomAD4 exome Cov.: 35
GnomAD4 exome
Cov.:
35
GnomAD4 genome ? Cov.: 31
GnomAD4 genome
?
Cov.:
31
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Short stature, facial dysmorphism, and skeletal anomalies with or without cardiac anomalies 1 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Feb 15, 2021 | - - |
Short stature, facial dysmorphism, and skeletal anomalies with or without cardiac anomalies Pathogenic:1
Likely pathogenic, criteria provided, single submitter | curation | SIB Swiss Institute of Bioinformatics | Oct 15, 2018 | This variant is interpreted as Likely Pathogenic, for Short stature, facial dysmorphism, and skeletal anomalies with or without cardiac anomalies, autosomal dominant. The following ACMG Tag(s) were applied: PM2 => Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium. PVS1-Moderate => PVS1 downgraded in strength to Moderate (https://www.ncbi.nlm.nih.gov/pubmed/29198724). PM6 => Assumed de novo, but without confirmation of paternity and maternity (https://www.ncbi.nlm.nih.gov/pubmed/29198724). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
MutationTaster
Benign
D
Vest4
GERP RS
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at