9-123356289-A-AC
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Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PM2
The NM_173689.7(CRB2):c.34dup(p.Gln12ProfsTer100) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000721 in 1,386,422 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (no stars).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0000072 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
CRB2
NM_173689.7 frameshift
NM_173689.7 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.237
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]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 10 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 40 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
|---|---|---|---|---|---|---|---|
| CRB2 | NM_173689.7 | c.34dup | p.Gln12ProfsTer100 | frameshift_variant | 1/13 | ENST00000373631.8 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| CRB2 | ENST00000373631.8 | c.34dup | p.Gln12ProfsTer100 | frameshift_variant | 1/13 | 1 | NM_173689.7 | P1 | |
| CRB2 | ENST00000359999.7 | c.34dup | p.Gln12ProfsTer100 | frameshift_variant | 1/10 | 2 |
Frequencies
GnomAD3 genomes 0.00000660 AC: 1AN: 151600Hom.: 0 Cov.: 31
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GnomAD4 exome AF: 0.00000721 AC: 10AN: 1386422Hom.: 0 Cov.: 32 AF XY: 0.0000102 AC XY: 7AN XY: 683928
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GnomAD4 genome 0.00000660 AC: 1AN: 151600Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1AN XY: 74002
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Data not reliable, filtered out with message: AS_VQSR
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
not provided Uncertain:1
| Uncertain significance, no assertion criteria provided | research | Gharavi Laboratory, Columbia University | Sep 16, 2018 | - - |
Computational scores
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at