Variant 20-46174852-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_021248.3(CDH22):c.2141C>G(p.Ser714Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000086 ( 0 hom., cov: 30)

Exomes 𝑓: 0.016 ( 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: 0.504

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 -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.18740019).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CDH22	NM_021248.3 linkuse as main transcript	c.2141C>G	p.Ser714Trp	missense_variant	12/12	ENST00000537909.4
CDH22	XM_011528994.3 linkuse as main transcript	c.2141C>G	p.Ser714Trp	missense_variant	12/12
CDH22	XM_047440373.1 linkuse as main transcript	c.1901C>G	p.Ser634Trp	missense_variant	10/10
CDH22	XM_024451966.2 linkuse as main transcript	c.1778C>G	p.Ser593Trp	missense_variant	12/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDH22	ENST00000537909.4 linkuse as main transcript	c.2141C>G	p.Ser714Trp	missense_variant	12/12	2	NM_021248.3	P1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

115624

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0000646

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000175

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000256

Gnomad SAS

AF:

0.000301

Gnomad FIN

AF:

0.000287

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000372

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000394

AC:

AN:

25404

Hom.:

AF XY:

0.0000634

AC XY:

AN XY:

15768

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000836

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0162

AC:

4717

AN:

290714

Hom.:

Cov.:

AF XY:

0.0147

AC XY:

2125

AN XY:

144866

show subpopulations

Gnomad4 AFR exome

AF:

0.0168

Gnomad4 AMR exome

AF:

0.00222

Gnomad4 ASJ exome

AF:

0.00569

Gnomad4 EAS exome

AF:

0.00285

Gnomad4 SAS exome

AF:

0.00500

Gnomad4 FIN exome

AF:

0.000133

Gnomad4 NFE exome

AF:

0.0189

Gnomad4 OTH exome

AF:

0.0144

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000864

AC:

AN:

115678

Hom.:

Cov.:

AF XY:

0.000107

AC XY:

AN XY:

56224

show subpopulations

Gnomad4 AFR

AF:

0.0000645

Gnomad4 AMR

AF:

0.000175

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000257

Gnomad4 SAS

AF:

0.000301

Gnomad4 FIN

AF:

0.000287

Gnomad4 NFE

AF:

0.0000372

Gnomad4 OTH

AF:

0.00

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

Sep 15, 2021

The c.2141C>G (p.S714W) 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 2141, causing the serine (S) at amino acid position 714 to be replaced by a tryptophan (W). 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

0.15

BayesDel_addAF

Benign

-0.071

BayesDel_noAF

Benign

-0.34

Cadd

Benign

Dann

Benign

0.96

DEOGEN2

Benign

0.13

T;T

Eigen

Benign

-0.79

Eigen_PC

Benign

-0.95

FATHMM_MKL

Benign

0.055

M_CAP

Benign

0.013

MetaRNN

Benign

0.19

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

N;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-1.0

N;N

REVEL

Benign

0.12

Sift

Uncertain

0.0010

D;D

Sift4G

Uncertain

0.0050

D;D

Polyphen

0.85

P;P

Vest4

0.28

MVP

0.42

ClinPred

0.24

GERP RS

-0.026

Varity_R

0.11

gMVP

0.27

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