Genetic Variant NM_021248.3:c.2153C>G (chr20-46174840-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_021248.3(CDH22):c.2153C>G(p.Ala718Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A718P) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 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: 2.24

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: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.11458418).

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.2153C>G	p.Ala718Gly	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.2153C>G	p.Ala718Gly	missense	Exon 12 of 12	ENSP00000437790.1	Q9UJ99
CDH22	ENST00000946368.1		c.2153C>G	p.Ala718Gly	missense	Exon 12 of 12	ENSP00000616427.1
CDH22	ENST00000946370.1		c.2153C>G	p.Ala718Gly	missense	Exon 12 of 12	ENSP00000616429.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1204514

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

586248

African (AFR)

AF:

0.00

AC:

AN:

24508

American (AMR)

AF:

0.00

AC:

AN:

14200

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18194

East Asian (EAS)

AF:

0.00

AC:

AN:

26812

South Asian (SAS)

AF:

0.00

AC:

AN:

49112

European-Finnish (FIN)

AF:

0.00

AC:

AN:

28592

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3552

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

990348

Other (OTH)

AF:

0.00

AC:

AN:

49196

GnomAD4 genome

Cov.:

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

0.054

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.45

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.018

Eigen

Benign

-0.71

Eigen_PC

Benign

-0.66

FATHMM_MKL

Benign

0.022

LIST_S2

Benign

0.32

M_CAP

Uncertain

0.17

MetaRNN

Benign

0.11

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.55

PhyloP100

2.2

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-0.92

REVEL

Benign

0.065

Sift

Benign

0.42

Sift4G

Benign

0.48

Polyphen

0.0010

Vest4

0.16

MutPred

0.44

Gain of catalytic residue at S720 (P = 0.1739)

MVP

0.43

ClinPred

0.18

GERP RS

2.1

Varity_R

0.12

gMVP

0.26

Mutation Taster

=92/8

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over