14-23049066-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_144985.4(CDH24):​c.1807G>A​(p.Ala603Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00106 in 1,612,778 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00060 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0011 ( 4 hom. )

Consequence

CDH24
NM_144985.4 missense

Scores

2
7
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.16
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.2099019).
BS2
High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CDH24NM_144985.4 linkc.1807G>A p.Ala603Thr missense_variant Exon 11 of 13 ENST00000487137.7 NP_659422.2 Q86UP0-2
CDH24NM_022478.4 linkc.1921G>A p.Ala641Thr missense_variant Exon 12 of 14 NP_071923.2 Q86UP0-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CDH24ENST00000487137.7 linkc.1807G>A p.Ala603Thr missense_variant Exon 11 of 13 5 NM_144985.4 ENSP00000434821.2 Q86UP0-2

Frequencies

GnomAD3 genomes
AF:
0.000604
AC:
92
AN:
152258
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000458
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00104
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.000382
AC:
94
AN:
246016
Hom.:
0
AF XY:
0.000410
AC XY:
55
AN XY:
133986
show subpopulations
Gnomad AFR exome
AF:
0.000128
Gnomad AMR exome
AF:
0.000116
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:
0.000785
Gnomad OTH exome
AF:
0.000330
GnomAD4 exome
AF:
0.00111
AC:
1624
AN:
1460402
Hom.:
4
Cov.:
32
AF XY:
0.00109
AC XY:
791
AN XY:
726506
show subpopulations
Gnomad4 AFR exome
AF:
0.000299
Gnomad4 AMR exome
AF:
0.000134
Gnomad4 ASJ exome
AF:
0.0000383
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.0000191
Gnomad4 NFE exome
AF:
0.00139
Gnomad4 OTH exome
AF:
0.000878
GnomAD4 genome
AF:
0.000604
AC:
92
AN:
152376
Hom.:
0
Cov.:
33
AF XY:
0.000564
AC XY:
42
AN XY:
74514
show subpopulations
Gnomad4 AFR
AF:
0.000457
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00104
Gnomad4 OTH
AF:
0.000473
Alfa
AF:
0.000640
Hom.:
0
Bravo
AF:
0.000582
TwinsUK
AF:
0.00108
AC:
4
ALSPAC
AF:
0.00104
AC:
4
ESP6500AA
AF:
0.000454
AC:
2
ESP6500EA
AF:
0.000465
AC:
4
ExAC
AF:
0.000363
AC:
44
EpiCase
AF:
0.000709
EpiControl
AF:
0.000712

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Aug 13, 2021
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1921G>A (p.A641T) alteration is located in exon 12 (coding exon 11) of the CDH24 gene. This alteration results from a G to A substitution at nucleotide position 1921, causing the alanine (A) at amino acid position 641 to be replaced by a threonine (T). 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
0.11
BayesDel_addAF
Benign
-0.17
T
BayesDel_noAF
Uncertain
-0.080
CADD
Pathogenic
26
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.098
.;T;.;T
Eigen
Uncertain
0.56
Eigen_PC
Uncertain
0.58
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.96
D;D;.;.
M_CAP
Benign
0.033
D
MetaRNN
Benign
0.21
T;T;T;T
MetaSVM
Benign
-0.51
T
MutationAssessor
Uncertain
2.7
.;M;.;M
PrimateAI
Uncertain
0.66
T
PROVEAN
Uncertain
-3.3
D;D;D;D
REVEL
Benign
0.29
Sift
Benign
0.057
T;T;T;T
Sift4G
Benign
0.073
T;T;T;T
Polyphen
0.97
D;D;D;D
Vest4
0.73
MVP
0.83
MPC
1.1
ClinPred
0.24
T
GERP RS
4.9
Varity_R
0.31
gMVP
0.90

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs200471169; hg19: chr14-23518275; COSMIC: COSV57458961; COSMIC: COSV57458961; API