Genetic Variant CDH24:p.Ala700Thr (chr14-23048228-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_144985.4(CDH24):c.2098G>A(p.Ala700Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000276 in 1,302,208 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 (★).

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

CDH24
NM_144985.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.581

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.07169908).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144985.4. 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
	CDH24	NM_144985.4	MANE Select	c.2098G>A	p.Ala700Thr	missense	Exon 12 of 13	NP_659422.2
	CDH24	NM_022478.4		c.2212G>A	p.Ala738Thr	missense	Exon 13 of 14	NP_071923.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CDH24	ENST00000487137.7	TSL:5 MANE Select	c.2098G>A	p.Ala700Thr	missense	Exon 12 of 13	ENSP00000434821.2	Q86UP0-2
CDH24	ENST00000267383.5	TSL:1	c.2212G>A	p.Ala738Thr	missense	Exon 12 of 12	ENSP00000267383.5	Q86UP0-1
CDH24	ENST00000554034.5	TSL:1	c.2098G>A	p.Ala700Thr	missense	Exon 11 of 11	ENSP00000452493.1	Q86UP0-2

Frequencies

GnomAD3 genomes

AF:

0.000146

AC:

AN:

150468

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000535

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

GnomAD2 exomes

AF:

0.0000711

AC:

AN:

14074

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00121

Gnomad ASJ exome

AF:

0.00

Gnomad EAS 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:

0.0000113

AC:

AN:

1151632

Hom.:

Cov.:

AF XY:

0.0000125

AC XY:

AN XY:

558478

show subpopulations

African (AFR)

AF:

0.000404

AC:

AN:

22252

American (AMR)

AF:

0.000335

AC:

AN:

8964

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14830

East Asian (EAS)

AF:

0.00

AC:

AN:

24136

South Asian (SAS)

AF:

0.00

AC:

AN:

42766

European-Finnish (FIN)

AF:

0.0000320

AC:

AN:

31220

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3076

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

958590

Other (OTH)

AF:

0.00

AC:

AN:

45798

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000153

AC:

AN:

150576

Hom.:

Cov.:

AF XY:

0.0000816

AC XY:

AN XY:

73572

show subpopulations

African (AFR)

AF:

0.000557

AC:

AN:

41268

American (AMR)

AF:

0.00

AC:

AN:

15130

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3452

East Asian (EAS)

AF:

0.00

AC:

AN:

5124

South Asian (SAS)

AF:

0.00

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9976

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67526

Other (OTH)

AF:

0.00

AC:

AN:

2084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.000166

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

0.093

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.39

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.0010

Eigen

Benign

-0.86

Eigen_PC

Benign

-0.77

FATHMM_MKL

Benign

0.34

LIST_S2

Benign

0.32

M_CAP

Pathogenic

0.37

MetaRNN

Benign

0.072

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.71

PhyloP100

0.58

PrimateAI

Pathogenic

0.91

PROVEAN

Benign

0.59

REVEL

Benign

0.056

Sift

Benign

0.50

Sift4G

Benign

0.58

Polyphen

0.0

Vest4

0.19

MutPred

0.35

Gain of catalytic residue at P734 (P = 5e-04)

MVP

0.66

MPC

1.5

ClinPred

0.043

GERP RS

3.0

Varity_R

0.064

gMVP

0.21

Mutation Taster

=90/10

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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over