Variant 20-46174648-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_021248.3(CDH22):c.2345C>T(p.Ala782Val) variant causes a missense change. The variant allele was found at a frequency of 0.00538 in 1,554,918 control chromosomes in the GnomAD database, including 355 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.028 ( 199 hom., cov: 32)

Exomes 𝑓: 0.0030 ( 156 hom. )

Consequence

CDH22
NM_021248.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 4.07

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0022613704).

BP6

Variant 20-46174648-G-A is Benign according to our data. Variant chr20-46174648-G-A is described in ClinVar as [Benign]. Clinvar id is 1236592.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0937 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CDH22	NM_021248.3 linkuse as main transcript	c.2345C>T	p.Ala782Val	missense_variant	12/12	ENST00000537909.4
CDH22	XM_011528994.3 linkuse as main transcript	c.2345C>T	p.Ala782Val	missense_variant	12/12
CDH22	XM_047440373.1 linkuse as main transcript	c.2105C>T	p.Ala702Val	missense_variant	10/10
CDH22	XM_024451966.2 linkuse as main transcript	c.1982C>T	p.Ala661Val	missense_variant	12/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDH22	ENST00000537909.4 linkuse as main transcript	c.2345C>T	p.Ala782Val	missense_variant	12/12	2	NM_021248.3	P1

Frequencies

GnomAD3 genomes

AF:

0.0277

AC:

4218

AN:

152186

Hom.:

199

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0963

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00995

Gnomad ASJ

AF:

0.00317

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.000309

Gnomad OTH

AF:

0.0182

GnomAD3 exomes

AF:

0.00660

AC:

1027

AN:

155500

Hom.:

AF XY:

0.00498

AC XY:

425

AN XY:

85278

show subpopulations

Gnomad AFR exome

AF:

0.0942

Gnomad AMR exome

AF:

0.00539

Gnomad ASJ exome

AF:

0.00300

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000423

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000327

Gnomad OTH exome

AF:

0.00296

GnomAD4 exome

AF:

0.00295

AC:

4141

AN:

1402624

Hom.:

156

Cov.:

AF XY:

0.00257

AC XY:

1781

AN XY:

693766

show subpopulations

Gnomad4 AFR exome

AF:

0.0971

Gnomad4 AMR exome

AF:

0.00624

Gnomad4 ASJ exome

AF:

0.00306

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000237

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000215

Gnomad4 OTH exome

AF:

0.00662

GnomAD4 genome

AF:

0.0277

AC:

4223

AN:

152294

Hom.:

199

Cov.:

AF XY:

0.0265

AC XY:

1974

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.0961

Gnomad4 AMR

AF:

0.00993

Gnomad4 ASJ

AF:

0.00317

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000309

Gnomad4 OTH

AF:

0.0180

Alfa

AF:

0.00874

Hom.:

Bravo

AF:

0.0307

ESP6500AA

AF:

0.0885

AC:

361

ESP6500EA

AF:

0.000374

AC:

ExAC

AF:

0.00657

AC:

748

Asia WGS

AF:

0.00348

AC:

AN:

3464

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 15, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.30

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.18

T;T

Eigen

Benign

0.13

Eigen_PC

Benign

0.19

FATHMM_MKL

Benign

0.32

LIST_S2

Uncertain

0.95

.;D

MetaRNN

Benign

0.0023

T;T

MetaSVM

Benign

-0.69

MutationAssessor

Uncertain

2.4

M;M

MutationTaster

Benign

0.0014

P;P

PrimateAI

Pathogenic

0.82

PROVEAN

Uncertain

-3.4

D;D

REVEL

Uncertain

0.35

Sift

Uncertain

0.0070

D;D

Sift4G

Uncertain

0.014

D;D

Polyphen

0.23

B;B

Vest4

0.092

MVP

0.70

ClinPred

0.030

GERP RS

3.8

Varity_R

0.29

gMVP

0.70

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over