Variant chr20-46174864-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_021248.3(CDH22):c.2129C>G(p.Ala710Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000087 ( 0 hom., cov: 27)

Exomes 𝑓: 0.0093 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CDH22
NM_021248.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0340

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 Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.06689039).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CDH22	NM_021248.3 linkuse as main transcript	c.2129C>G	p.Ala710Gly	missense_variant	12/12	ENST00000537909.4
CDH22	XM_011528994.3 linkuse as main transcript	c.2129C>G	p.Ala710Gly	missense_variant	12/12
CDH22	XM_047440373.1 linkuse as main transcript	c.1889C>G	p.Ala630Gly	missense_variant	10/10
CDH22	XM_024451966.2 linkuse as main transcript	c.1766C>G	p.Ala589Gly	missense_variant	12/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDH22	ENST00000537909.4 linkuse as main transcript	c.2129C>G	p.Ala710Gly	missense_variant	12/12	2	NM_021248.3	P1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

91618

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0000407

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000627

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000421

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000464

Gnomad OTH

AF:

0.000817

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00926

AC:

1457

AN:

157282

Hom.:

Cov.:

AF XY:

0.00831

AC XY:

681

AN XY:

81912

show subpopulations

Gnomad4 AFR exome

AF:

0.00541

Gnomad4 AMR exome

AF:

0.000423

Gnomad4 ASJ exome

AF:

0.00108

Gnomad4 EAS exome

AF:

0.00149

Gnomad4 SAS exome

AF:

0.00182

Gnomad4 FIN exome

AF:

0.000403

Gnomad4 NFE exome

AF:

0.0121

Gnomad4 OTH exome

AF:

0.00998

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000873

AC:

AN:

91614

Hom.:

Cov.:

AF XY:

0.0000898

AC XY:

AN XY:

44558

show subpopulations

Gnomad4 AFR

AF:

0.0000406

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000629

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000421

Gnomad4 NFE

AF:

0.0000464

Gnomad4 OTH

AF:

0.000814

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 09, 2022

The c.2129C>G (p.A710G) alteration is located in exon 11 (coding exon 11) of the CDH22 gene. This alteration results from a C to G substitution at nucleotide position 2129, causing the alanine (A) at amino acid position 710 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.048

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.51

CADD

Benign

0.092

DANN

Benign

0.62

DEOGEN2

Benign

0.015

T;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0076

LIST_S2

Benign

0.21

.;T

M_CAP

Uncertain

0.19

MetaRNN

Benign

0.067

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.34

N;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.79

PROVEAN

Benign

-0.24

N;N

REVEL

Benign

0.064

Sift

Benign

0.57

T;T

Sift4G

Uncertain

0.0020

D;D

Polyphen

0.0

B;B

Vest4

0.20

MVP

0.25

ClinPred

0.072

GERP RS

-1.8

Varity_R

0.030

gMVP

0.26

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