Genetic Variant CDH24:p.Gly754Asp (chr14-23048065-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_144985.4(CDH24):c.2261G>A(p.Gly754Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000258 in 1,434,588 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

CDH24
NM_144985.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.81

Variant links:

Genes affected

CDH24 (HGNC:14265): (cadherin 24) Enables several functions, including alpha-catenin binding activity; beta-catenin binding activity; and delta-catenin binding activity. Acts upstream of or within cell-cell adhesion. Located in cell-cell junction. [provided by Alliance of Genome Resources, Apr 2022]

CDH24 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.20844978).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH24	NM_144985.4 link	c.2261G>A	p.Gly754Asp	missense_variant	Exon 12 of 13	ENST00000487137.7	NP_659422.2	Q86UP0-2
CDH24	NM_022478.4 link	c.2375G>A	p.Gly792Asp	missense_variant	Exon 13 of 14		NP_071923.2	Q86UP0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDH24	ENST00000487137.7 link	c.2261G>A	p.Gly754Asp	missense_variant	Exon 12 of 13	5	NM_144985.4	ENSP00000434821.2		Q86UP0-2

Frequencies

GnomAD3 genomes

AF:

0.000138

AC:

AN:

151718

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000435

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.0000523

AC:

AN:

57384

Hom.:

AF XY:

0.00

AC XY:

AN XY:

34022

show subpopulations

Gnomad AFR exome

AF:

0.00121

Gnomad AMR exome

AF:

0.000191

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000125

AC:

AN:

1282870

Hom.:

Cov.:

AF XY:

0.0000111

AC XY:

AN XY:

632568

show subpopulations

Gnomad4 AFR exome

AF:

0.000358

Gnomad4 AMR exome

AF:

0.000193

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000145

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000382

GnomAD4 genome

AF:

0.000138

AC:

AN:

151718

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74092

show subpopulations

Gnomad4 AFR

AF:

0.000435

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000479

Alfa

AF:

0.000214

Hom.:

Bravo

AF:

0.000174

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 22, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2375G>A (p.G792D) alteration is located in exon 13 (coding exon 12) of the CDH24 gene. This alteration results from a G to A substitution at nucleotide position 2375, causing the glycine (G) at amino acid position 792 to be replaced by an aspartic acid (D). 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

0.13

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.26

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0011

.;T;.;.;T

Eigen

Benign

-0.080

Eigen_PC

Benign

0.019

FATHMM_MKL

Benign

0.74

LIST_S2

Benign

0.74

T;T;T;.;.

M_CAP

Pathogenic

0.73

MetaRNN

Benign

0.21

T;T;T;T;T

MetaSVM

Benign

-0.39

MutationAssessor

Benign

0.49

.;N;.;.;N

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

0.73

N;N;.;N;N

REVEL

Benign

0.23

Sift

Benign

0.11

T;T;.;T;T

Sift4G

Benign

0.094

T;T;T;T;T

Polyphen

0.035

B;D;.;B;D

Vest4

0.23

MutPred

0.48

.;Gain of catalytic residue at A787 (P = 0.0215);.;.;Gain of catalytic residue at A787 (P = 0.0215);

MVP

0.86

MPC

2.6

ClinPred

0.040

GERP RS

4.0

Varity_R

0.11

gMVP

0.26

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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