dbSNP rs2425785: CDH22:c.1033-123C>G (chr20-46210683-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_021248.3(CDH22):c.1033-123C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.362 in 911,410 control chromosomes in the GnomAD database, including 61,225 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.39 ( 11771 hom., cov: 31)

Exomes 𝑓: 0.36 ( 49454 hom. )

Consequence

CDH22
NM_021248.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.29

Publications

4 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:

LOC124904916 (HGNC:):

LOC124904916 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.482 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH22	NM_021248.3 link	c.1033-123C>G		intron_variant	Intron 6 of 11	ENST00000537909.4	NP_067071.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDH22	ENST00000537909.4 link	c.1033-123C>G		intron_variant	Intron 6 of 11	2	NM_021248.3	ENSP00000437790.1
CDH22	ENST00000474438.1 link	n.901-123C>G		intron_variant	Intron 4 of 4	1

Frequencies

GnomAD3 genomes

AF:

0.387

AC:

58661

AN:

151774

Hom.:

11758

Cov.:

show subpopulations

Gnomad AFR

AF:

0.488

Gnomad AMI

AF:

0.345

Gnomad AMR

AF:

0.306

Gnomad ASJ

AF:

0.345

Gnomad EAS

AF:

0.276

Gnomad SAS

AF:

0.430

Gnomad FIN

AF:

0.378

Gnomad MID

AF:

0.383

Gnomad NFE

AF:

0.353

Gnomad OTH

AF:

0.362

GnomAD4 exome

AF:

0.358

AC:

271586

AN:

759518

Hom.:

49454

AF XY:

0.360

AC XY:

135163

AN XY:

375692

show subpopulations

African (AFR)

AF:

0.487

AC:

7615

AN:

15646

American (AMR)

AF:

0.308

AC:

3546

AN:

11516

Ashkenazi Jewish (ASJ)

AF:

0.362

AC:

4745

AN:

13114

East Asian (EAS)

AF:

0.280

AC:

7532

AN:

26926

South Asian (SAS)

AF:

0.451

AC:

11929

AN:

26458

European-Finnish (FIN)

AF:

0.386

AC:

15413

AN:

39902

Middle Eastern (MID)

AF:

0.368

AC:

973

AN:

2642

European-Non Finnish (NFE)

AF:

0.352

AC:

207803

AN:

589992

Other (OTH)

AF:

0.361

AC:

12030

AN:

33322

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

8755

17511

26266

35022

43777

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6372

12744

19116

25488

31860

<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:

0.387

AC:

58717

AN:

151892

Hom.:

11771

Cov.:

AF XY:

0.382

AC XY:

28369

AN XY:

74236

show subpopulations

African (AFR)

AF:

0.488

AC:

20203

AN:

41402

American (AMR)

AF:

0.305

AC:

4657

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.345

AC:

1195

AN:

3464

East Asian (EAS)

AF:

0.276

AC:

1418

AN:

5146

South Asian (SAS)

AF:

0.431

AC:

2078

AN:

4820

European-Finnish (FIN)

AF:

0.378

AC:

3990

AN:

10558

Middle Eastern (MID)

AF:

0.398

AC:

117

AN:

294

European-Non Finnish (NFE)

AF:

0.353

AC:

23976

AN:

67910

Other (OTH)

AF:

0.365

AC:

768

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1823

3646

5469

7292

9115

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

572

1144

1716

2288

2860

<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:

0.365

Hom.:

1260

Bravo

AF:

0.385

Asia WGS

AF:

0.360

AC:

1254

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.12

(source)

DANN

Benign

0.67

PhyloP100

-1.3

Mutation Taster

=100/0

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over