X-153504675-AG-A

Variant summary

Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1_Strong PM2 PP5_Moderate

The NM_001711.6(BGN):c.46del(p.Ala16ProfsTer20) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★).

• Frequency: Genomes: not found (cov: 25)
• Consequence: BGN NM_001711.6 frameshift
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 1.42

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]

ACMG classification

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 9 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant X-153504675-AG-A is Pathogenic according to our data. Variant chrX-153504675-AG-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 2663753.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.46del	p.Ala16ProfsTer20	frameshift_variant	2/8	ENST00000331595.9
BGN	XM_017029724.3	c.46del	p.Ala16ProfsTer20	frameshift_variant	1/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BGN	ENST00000331595.9	c.46del	p.Ala16ProfsTer20	frameshift_variant	2/8	1	NM_001711.6	P1
BGN	ENST00000431891.1	c.46del	p.Ala16ProfsTer20	frameshift_variant	2/5	5
BGN	ENST00000472615.5	n.190del		non_coding_transcript_exon_variant	2/8	5
BGN	ENST00000480756.1	n.188del		non_coding_transcript_exon_variant	2/8	5

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 25

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

Meester-Loeys syndrome Pathogenic:1

Likely pathogenic, criteria provided, single submitter

in vitro;research

Centre of Medical Genetics, University of Antwerp

Oct 20, 2023

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Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-152770133;