X-153504689-G-GAA

Position:

• chrX-153504689-G-GAA

Variant summary

Our verdict is Pathogenic. Variant got 14 ACMG points: 14P and 0B. PVS1_Strong PM2 PP5_Very_Strong

The ENST00000331595.9(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 ENST00000331595.9 frameshift
• Clinical Significance: Likely pathogenic criteria provided, multiple submitters, no conflicts P:2
• 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]

ACMG classification

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	Protein	UniProt
BGN	NM_001711.6	c.59_60insAA	p.Gln21SerfsTer16	frameshift_variant	2/8	ENST00000331595.9	NP_001702.1
BGN	XM_017029724.3	c.59_60insAA	p.Gln21SerfsTer16	frameshift_variant	1/7		XP_016885213.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BGN	ENST00000331595.9	c.59_60insAA	p.Gln21SerfsTer16	frameshift_variant	2/8	1	NM_001711.6	ENSP00000327336	P1
BGN	ENST00000431891.1	c.59_60insAA	p.Gln21SerfsTer16	frameshift_variant	2/5	5		ENSP00000402525
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

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 24

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Meester-Loeys syndrome Pathogenic:1

Likely pathogenic, criteria provided, single submitter

research

Centre of Medical Genetics, University of Antwerp

Oct 20, 2023

- -

not provided Pathogenic:1

Likely pathogenic, criteria provided, single submitter

clinical testing

Blueprint Genetics

Jul 04, 2018

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1602981441; hg19: chrX-152770147;