Genetic Variant CDH22:p.Gly708Glu (chr20-46174870-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_021248.3(CDH22):c.2123G>A(p.Gly708Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000156 in 1,348,194 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

CDH22
NM_021248.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.428

Publications

0 publications found

Variant links:

Genes affected

CDH22 (HGNC:13251): (cadherin 22) This gene is a member of the cadherin superfamily. The gene product is composed of five cadherin repeat domains and a cytoplasmic tail similar to the highly conserved cytoplasmic region of classical cadherins. Expressed predominantly in the brain, this putative calcium-dependent cell adhesion protein may play an important role in morphogenesis and tissue formation in neural and non-neural cells during development and maintenance of the brain and neuroendocrine organs. [provided by RefSeq, Jul 2008]

CDH22 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0076978207).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021248.3. 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
	CDH22	NM_021248.3	MANE Select	c.2123G>A	p.Gly708Glu	missense	Exon 12 of 12	NP_067071.1	Q9UJ99

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CDH22	ENST00000537909.4	TSL:2 MANE Select	c.2123G>A	p.Gly708Glu	missense	Exon 12 of 12	ENSP00000437790.1	Q9UJ99
CDH22	ENST00000946368.1		c.2123G>A	p.Gly708Glu	missense	Exon 12 of 12	ENSP00000616427.1
CDH22	ENST00000946370.1		c.2123G>A	p.Gly708Glu	missense	Exon 12 of 12	ENSP00000616429.1

Frequencies

GnomAD3 genomes

AF:

0.0000795

AC:

AN:

150922

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000266

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000660

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000552

AC:

AN:

72452

AF XY:

0.0000236

show subpopulations

Gnomad AFR exome

AF:

0.00174

Gnomad AMR exome

AF:

0.0000966

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:

0.00000752

AC:

AN:

1197164

Hom.:

Cov.:

AF XY:

0.00000516

AC XY:

AN XY:

581586

show subpopulations

African (AFR)

AF:

0.000157

AC:

AN:

25478

American (AMR)

AF:

0.0000506

AC:

AN:

19780

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20130

East Asian (EAS)

AF:

0.00

AC:

AN:

27238

South Asian (SAS)

AF:

0.00

AC:

AN:

44892

European-Finnish (FIN)

AF:

0.00

AC:

AN:

27218

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3414

European-Non Finnish (NFE)

AF:

0.00000306

AC:

AN:

980358

Other (OTH)

AF:

0.0000206

AC:

AN:

48656

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.558

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:

0.0000795

AC:

AN:

151030

Hom.:

Cov.:

AF XY:

0.000122

AC XY:

AN XY:

73804

show subpopulations

African (AFR)

AF:

0.000266

AC:

AN:

41406

American (AMR)

AF:

0.0000659

AC:

AN:

15178

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3456

East Asian (EAS)

AF:

0.00

AC:

AN:

5160

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10072

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67632

Other (OTH)

AF:

0.00

AC:

AN:

2098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.583

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:

0.0000712

Hom.:

Bravo

AF:

0.0000945

ExAC

AF:

0.0000182

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.44

CADD

Benign

0.92

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.12

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0014

LIST_S2

Benign

0.30

M_CAP

Benign

0.050

MetaRNN

Benign

0.0077

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

PhyloP100

0.43

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-0.50

REVEL

Benign

0.097

Sift

Benign

0.16

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.20

MutPred

0.44

Loss of glycosylation at S705 (P = 0.0784)

MVP

0.26

ClinPred

0.022

GERP RS

-1.0

Varity_R

0.082

gMVP

0.23

Mutation Taster

=93/7

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over