X-153504636-G-A
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1_StrongPM2PP5_Moderate
The NM_001711.6(BGN):c.5G>A(p.Trp2Ter) 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: 25)
Consequence
BGN
NM_001711.6 stop_gained
NM_001711.6 stop_gained
Scores
1
4
Clinical Significance
Conservation
PhyloP100: -1.23
Genes affected
BGN (HGNC:1044): (biglycan) This gene encodes a member of the small leucine-rich proteoglycan (SLRP) family of proteins. The encoded preproprotein is proteolytically processed to generate the mature protein, which plays a role in bone growth, muscle development and regeneration, and collagen fibril assembly in multiple tissues. This protein may also regulate inflammation and innate immunity. Additionally, the encoded protein may contribute to atherosclerosis and aortic valve stenosis in human patients. This gene and the related gene decorin are thought to be the result of a gene duplication. [provided by RefSeq, Nov 2015]
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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 located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 10 pathogenic variants in the truncated region.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant X-153504636-G-A is Pathogenic according to our data. Variant chrX-153504636-G-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 265794.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BGN | NM_001711.6 | c.5G>A | p.Trp2Ter | stop_gained | 2/8 | ENST00000331595.9 | |
BGN | XM_017029724.3 | c.5G>A | p.Trp2Ter | stop_gained | 1/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BGN | ENST00000331595.9 | c.5G>A | p.Trp2Ter | stop_gained | 2/8 | 1 | NM_001711.6 | P1 | |
BGN | ENST00000431891.1 | c.5G>A | p.Trp2Ter | stop_gained | 2/5 | 5 | |||
BGN | ENST00000472615.5 | n.149G>A | non_coding_transcript_exon_variant | 2/8 | 5 | ||||
BGN | ENST00000480756.1 | n.147G>A | non_coding_transcript_exon_variant | 2/8 | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 25
GnomAD3 genomes
?
Cov.:
25
GnomAD4 exome Cov.: 30
GnomAD4 exome
Cov.:
30
GnomAD4 genome ? Cov.: 25
GnomAD4 genome
?
Cov.:
25
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:3
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Meester-Loeys syndrome Pathogenic:2
Likely pathogenic, criteria provided, single submitter | research | Centre of Medical Genetics, University of Antwerp | Mar 01, 2021 | PM2, PVS1 - |
Pathogenic, no assertion criteria provided | literature only | OMIM | May 10, 2017 | - - |
Familial thoracic aortic aneurysm and aortic dissection Pathogenic:1
Pathogenic, no assertion criteria provided | research | Centre of Medical Genetics, University of Antwerp | - | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Benign
Cadd
Pathogenic
Dann
Benign
FATHMM_MKL
Benign
N
MutationTaster
Benign
A;N
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