Variant 9-123356303-G-GCCTCTGT details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5

The NM_173689.7(CRB2):c.47_53dup(p.Leu19CysfsTer95) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000215 in 1,393,830 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (no stars).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000022 ( 0 hom. )

Consequence

CRB2
NM_173689.7 frameshift

Scores

Not classified

Clinical Significance

Likely pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: -1.08

Variant links:

Genes affected

CRB2 (HGNC:18688): (crumbs cell polarity complex component 2) This gene encodes a member of a family of proteins that are components of the Crumbs cell polarity complex. In mammals, members of this family are thought to play a role in many cellular processes in early embryonic development. A similar protein in Drosophila determines apicobasal polarity in embryonic epithelial cells. Mutations in this gene are associated with focal segmental glomerulosclerosis 9, and with ventriculomegaly with cystic kidney disease. [provided by RefSeq, Aug 2016]

CRB2 links:

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ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 11 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 39 pathogenic variants in the truncated region.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 9-123356303-G-GCCTCTGT is Pathogenic according to our data. Variant chr9-123356303-G-GCCTCTGT is described in ClinVar as [Likely_pathogenic]. Clinvar id is 829963.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRB2	NM_173689.7 linkuse as main transcript	c.47_53dup	p.Leu19CysfsTer95	frameshift_variant	1/13	ENST00000373631.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRB2	ENST00000373631.8 linkuse as main transcript	c.47_53dup	p.Leu19CysfsTer95	frameshift_variant	1/13	1	NM_173689.7	P1	Q5IJ48-1
CRB2	ENST00000359999.7 linkuse as main transcript	c.47_53dup	p.Leu19CysfsTer95	frameshift_variant	1/10	2			Q5IJ48-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000215

AC:

AN:

1393830

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

687530

show subpopulations

Gnomad4 AFR exome

AF:

0.0000318

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000186

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Focal segmental glomerulosclerosis 9

Pathogenic:1

Likely pathogenic, no assertion criteria provided

clinical testing

Bioscientia Institut fuer Medizinische Diagnostik GmbH, Sonic Healthcare

May 16, 2019

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Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over