9-123356343-C-T

Variant names:

• chr9-123356343-C-T
• NM_173689.7:c.83C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: CRB2 NM_173689.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.465

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17267042).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRB2	NM_173689.7	c.83C>T	p.Ser28Phe	missense_variant	Exon 1 of 13	ENST00000373631.8	NP_775960.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRB2	ENST00000373631.8	c.83C>T	p.Ser28Phe	missense_variant	Exon 1 of 13	1	NM_173689.7	ENSP00000362734.3
CRB2	ENST00000359999.7	c.83C>T	p.Ser28Phe	missense_variant	Exon 1 of 10	2		ENSP00000353092.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.17e-7 AC: 1 AN: 1394750 Hom.: 0 Cov.: 32 AF XY: 0.00000145 AC XY: 1 AN XY: 688002

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000127

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.093	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	18
DANN	Benign	0.96
DEOGEN2	Benign	0.045	.;T
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.047	N
LIST_S2	Benign	0.40	T;T
M_CAP	Pathogenic	0.31	D
MetaRNN	Benign	0.17	T;T
MetaSVM	Benign	-0.59	T
MutationAssessor	Benign	1.2	L;L
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-0.64	N;N
REVEL	Benign	0.24
Sift	Benign	0.069	T;T
Sift4G	Uncertain	0.0020	D;D
Polyphen		0.0	B;B
Vest4		0.11
MutPred		0.54		Loss of disorder (P = 0.0065);Loss of disorder (P = 0.0065);
MVP		0.76
MPC		0.30
ClinPred		0.069	T
GERP RS		1.2
Varity_R		0.070
gMVP		0.38

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-126118622; COSMIC: COSV105272022;