chr14-23048426-C-T

Variant summary

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

The NM_144985.4(CDH24):​c.1900G>A​(p.Val634Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000891 in 1,459,852 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

CDH24
NM_144985.4 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.585
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]

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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=0.06834608).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CDH24NM_144985.4 linkc.1900G>A p.Val634Ile missense_variant Exon 12 of 13 ENST00000487137.7 NP_659422.2 Q86UP0-2
CDH24NM_022478.4 linkc.2014G>A p.Val672Ile missense_variant Exon 13 of 14 NP_071923.2 Q86UP0-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CDH24ENST00000487137.7 linkc.1900G>A p.Val634Ile missense_variant Exon 12 of 13 5 NM_144985.4 ENSP00000434821.2 Q86UP0-2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000807
AC:
2
AN:
247788
Hom.:
0
AF XY:
0.0000148
AC XY:
2
AN XY:
134688
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:
0.0000179
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000891
AC:
13
AN:
1459852
Hom.:
0
Cov.:
34
AF XY:
0.0000110
AC XY:
8
AN XY:
726332
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000108
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.00000824
AC:
1
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jun 02, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.2014G>A (p.V672I) 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 2014, causing the valine (V) at amino acid position 672 to be replaced by an isoleucine (I). 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
0.14
BayesDel_addAF
Benign
-0.17
T
BayesDel_noAF
Benign
-0.49
CADD
Benign
18
DANN
Benign
0.92
DEOGEN2
Benign
0.00084
.;T;.;.;T
Eigen
Benign
-0.67
Eigen_PC
Benign
-0.51
FATHMM_MKL
Benign
0.35
N
LIST_S2
Benign
0.85
T;D;D;.;.
M_CAP
Benign
0.036
D
MetaRNN
Benign
0.068
T;T;T;T;T
MetaSVM
Benign
-0.85
T
MutationAssessor
Benign
-0.80
.;N;.;.;N
PrimateAI
Uncertain
0.56
T
PROVEAN
Benign
0.21
N;N;.;N;N
REVEL
Benign
0.18
Sift
Benign
1.0
T;T;.;T;T
Sift4G
Benign
1.0
T;T;T;T;T
Polyphen
0.23
B;P;.;B;P
Vest4
0.26
MutPred
0.46
.;Gain of catalytic residue at L673 (P = 0.0388);.;.;Gain of catalytic residue at L673 (P = 0.0388);
MVP
0.69
MPC
0.56
ClinPred
0.21
T
GERP RS
3.7
Varity_R
0.026
gMVP
0.49

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.

Other links and lift over

dbSNP: rs748984616; hg19: chr14-23517635; API