7-33905639-CTCTGGCTGA-AGACCAGAGCGGCG

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PVS1_Strong PM2 PP5

The NM_001365308.1(BMPER):c.26_35delinsAGACCAGAGCGGCG(p.Ala9GlufsTer44) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 29)
• Consequence: BMPER NM_001365308.1 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 3.89

Genes affected

BMPER (HGNC:24154): (BMP binding endothelial regulator) This gene encodes a secreted protein that interacts with, and inhibits bone morphogenetic protein (BMP) function. It has been shown to inhibit BMP2- and BMP4-dependent osteoblast differentiation and BMP-dependent differentiation of the chondrogenic cells. Mutations in this gene are associated with a lethal skeletal disorder, diaphanospondylodysostosis. [provided by RefSeq, Dec 2011]

ACMG classification

Verdict is Likely_pathogenic. Variant got 7 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 14 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 7-33905639-CTCTGGCTGA-AGACCAGAGCGGCG is Pathogenic according to our data. Variant chr7-33905639-CTCTGGCTGA-AGACCAGAGCGGCG is described in ClinVar as [Pathogenic]. Clinvar id is 30743.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BMPER	NM_001365308.1	c.26_35delinsAGACCAGAGCGGCG	p.Ala9GlufsTer44	frameshift_variant	1/15	ENST00000649409.2
BMPER	NM_001410872.1	c.26_35delinsAGACCAGAGCGGCG	p.Ala9GlufsTer44	frameshift_variant	1/14
BMPER	NM_133468.5	c.26_35delinsAGACCAGAGCGGCG	p.Ala9GlufsTer44	frameshift_variant	2/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BMPER	ENST00000649409.2	c.26_35delinsAGACCAGAGCGGCG	p.Ala9GlufsTer44	frameshift_variant	1/15		NM_001365308.1	P1

Frequencies

GnomAD3 genomes Cov.: 29

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 29

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Diaphanospondylodysostosis Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Oct 08, 2010

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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: chr7-33945251;