Genetic Variant NM_173689.7:c.83C>T (chr9-123356343-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_173689.7(CRB2):c.83C>T(p.Ser28Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000717 in 1,394,750 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S28Y) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

CRB2
NM_173689.7 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.465

Publications

0 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: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.17267042).

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.83C>T	p.Ser28Phe	missense	Exon 1 of 13	NP_775960.4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CRB2	ENST00000373631.8	TSL:1 MANE Select	c.83C>T	p.Ser28Phe	missense	Exon 1 of 13	ENSP00000362734.3	Q5IJ48-1
CRB2	ENST00000896215.1		c.83C>T	p.Ser28Phe	missense	Exon 1 of 13	ENSP00000566274.1
CRB2	ENST00000359999.7	TSL:2	c.83C>T	p.Ser28Phe	missense	Exon 1 of 10	ENSP00000353092.3	Q5IJ48-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.17e-7

AC:

AN:

1394750

Hom.:

Cov.:

AF XY:

0.00000145

AC XY:

AN XY:

688002

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31452

American (AMR)

AF:

0.00

AC:

AN:

35216

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25092

East Asian (EAS)

AF:

0.00

AC:

AN:

35590

South Asian (SAS)

AF:

0.0000127

AC:

AN:

78820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47372

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5678

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1077686

Other (OTH)

AF:

0.00

AC:

AN:

57844

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

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

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.093

BayesDel_noAF

Benign

-0.37

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.045

Eigen

Benign

-0.77

Eigen_PC

Benign

-0.82

FATHMM_MKL

Benign

0.047

LIST_S2

Benign

0.40

M_CAP

Pathogenic

0.31

MetaRNN

Benign

0.17

MetaSVM

Benign

-0.59

MutationAssessor

Benign

1.2

PhyloP100

0.47

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-0.64

REVEL

Benign

0.24

Sift

Benign

0.069

Sift4G

Uncertain

0.0020

Polyphen

0.0

Vest4

0.11

MutPred

0.54

Loss of disorder (P = 0.0065)

MVP

0.76

MPC

0.30

ClinPred

0.069

GERP RS

1.2

PromoterAI

0.058

Neutral

(source)

Varity_R

0.070

gMVP

0.38

Mutation Taster

=96/4

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over