X-153504689-G-GAA
Variant summary
Our verdict is Pathogenic. Variant got 14 ACMG points: 14P and 0B. PVS1_StrongPM2PP5_Very_Strong
The NM_001711.6(BGN):c.59_60insAA(p.Gln21SerfsTer16) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★★).
Frequency
Genomes: not found (cov: 24)
Consequence
BGN
NM_001711.6 frameshift
NM_001711.6 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 4.69
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 Pathogenic. Variant got 14 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 9 pathogenic variants in the truncated region.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant X-153504689-G-GAA is Pathogenic according to our data. Variant chrX-153504689-G-GAA is described in ClinVar as [Likely_pathogenic]. Clinvar id is 636703.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BGN | NM_001711.6 | c.59_60insAA | p.Gln21SerfsTer16 | frameshift_variant | 2/8 | ENST00000331595.9 | |
BGN | XM_017029724.3 | c.59_60insAA | p.Gln21SerfsTer16 | frameshift_variant | 1/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BGN | ENST00000331595.9 | c.59_60insAA | p.Gln21SerfsTer16 | frameshift_variant | 2/8 | 1 | NM_001711.6 | P1 | |
BGN | ENST00000431891.1 | c.59_60insAA | p.Gln21SerfsTer16 | frameshift_variant | 2/5 | 5 | |||
BGN | ENST00000472615.5 | n.203_204insAA | non_coding_transcript_exon_variant | 2/8 | 5 | ||||
BGN | ENST00000480756.1 | n.201_202insAA | non_coding_transcript_exon_variant | 2/8 | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 24
GnomAD3 genomes
?
Cov.:
24
GnomAD4 exome Cov.: 30
GnomAD4 exome
Cov.:
30
GnomAD4 genome ? Cov.: 24
GnomAD4 genome
?
Cov.:
24
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Blueprint Genetics | Jul 04, 2018 | - - |
Meester-Loeys syndrome Pathogenic:1
Likely pathogenic, criteria provided, single submitter | research | Centre of Medical Genetics, University of Antwerp | Oct 20, 2023 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at