rs879255251

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Pathogenic. The variant received 16 ACMG points: 16P and 0B. PVS1PP5_Very_Strong

The NM_173689.7(CRB2):c.3089_3104delGGCCCGGCGCGGCCCC(p.Arg1030LeufsTer106) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000386 in 1,374,404 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Likely pathogenic (★★). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000037 ( 0 hom. )

Consequence

CRB2
NM_173689.7 frameshift

Scores

Not classified

Clinical Significance

Pathogenic/Likely pathogenic criteria provided, multiple submitters, no conflicts P:4

Conservation

PhyloP100: 1.86

Publications

6 publications found

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 Gene-Disease associations (from GenCC):

focal segmental glomerulosclerosis 9
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae)
ventriculomegaly-cystic kidney disease
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp, G2P
familial idiopathic steroid-resistant nephrotic syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
retinitis pigmentosa
Inheritance: AR Classification: LIMITED Submitted by: G2P

CRB2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Pathogenic. The variant received 16 ACMG points.

PVS1

Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.

PP5

Variant 9-123373608-TGGCGCGGCCCCGGCCC-T is Pathogenic according to our data. Variant chr9-123373608-TGGCGCGGCCCCGGCCC-T is described in ClinVar as Pathogenic/Likely_pathogenic. ClinVar VariationId is 1324169.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173689.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRB2	NM_173689.7	MANE Select	c.3089_3104delGGCCCGGCGCGGCCCC	p.Arg1030LeufsTer106	frameshift	Exon 10 of 13	NP_775960.4
	CRB2	NR_104603.2		n.2203_2218delGGCCCGGCGCGGCCCC		non_coding_transcript_exon	Exon 5 of 9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CRB2	ENST00000373631.8	TSL:1 MANE Select	c.3089_3104delGGCCCGGCGCGGCCCC	p.Arg1030LeufsTer106	frameshift	Exon 10 of 13	ENSP00000362734.3	Q5IJ48-1
CRB2	ENST00000896215.1		c.3062_3077delGGCCCGGCGCGGCCCC	p.Arg1021LeufsTer106	frameshift	Exon 10 of 13	ENSP00000566274.1
CRB2	ENST00000359999.7	TSL:2	c.3089_3104delGGCCCGGCGCGGCCCC	p.Arg1030LeufsTer138	frameshift	Exon 10 of 10	ENSP00000353092.3	Q5IJ48-2

Frequencies

GnomAD3 genomes

AF:

0.0000528

AC:

AN:

151596

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000658

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000884

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00

AC:

AN:

28070

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000368

AC:

AN:

1222808

Hom.:

AF XY:

0.0000434

AC XY:

AN XY:

598848

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

24274

American (AMR)

AF:

0.00

AC:

AN:

12770

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17504

East Asian (EAS)

AF:

0.00

AC:

AN:

26936

South Asian (SAS)

AF:

0.0000369

AC:

AN:

54140

European-Finnish (FIN)

AF:

0.00

AC:

AN:

30096

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4906

European-Non Finnish (NFE)

AF:

0.0000419

AC:

AN:

1002278

Other (OTH)

AF:

0.0000200

AC:

AN:

49904

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000528

AC:

AN:

151596

Hom.:

Cov.:

AF XY:

0.0000405

AC XY:

AN XY:

74058

show subpopulations

African (AFR)

AF:

0.0000242

AC:

AN:

41368

American (AMR)

AF:

0.0000658

AC:

AN:

15208

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.00

AC:

AN:

4838

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10394

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000884

AC:

AN:

67842

Other (OTH)

AF:

0.00

AC:

AN:

2084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000529

ClinVar

ClinVar submissions

Significance:Pathogenic/Likely pathogenic

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

CRB2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.9

Mutation Taster

=11/189

disease causing (fs/PTC)

(source)

Splicing

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over