16-82858377-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001257.5(CDH13):ā€‹c.61T>Cā€‹(p.Ser21Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,780 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 (ā˜…).

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 6.9e-7 ( 0 hom. )

Consequence

CDH13
NM_001257.5 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.56
Variant links:
Genes affected
CDH13 (HGNC:1753): (cadherin 13) This gene encodes a member of the cadherin superfamily. The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety, rather than by a transmembrane domain. The protein lacks the cytoplasmic domain characteristic of other cadherins, and so is not thought to be a cell-cell adhesion glycoprotein. This protein acts as a negative regulator of axon growth during neural differentiation. It also protects vascular endothelial cells from apoptosis due to oxidative stress, and is associated with resistance to atherosclerosis. The gene is hypermethylated in many types of cancer. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, May 2011]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.2821443).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CDH13NM_001257.5 linkc.61T>C p.Ser21Pro missense_variant Exon 2 of 14 ENST00000567109.6 NP_001248.1 P55290-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CDH13ENST00000567109.6 linkc.61T>C p.Ser21Pro missense_variant Exon 2 of 14 1 NM_001257.5 ENSP00000479395.1 P55290-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.85e-7
AC:
1
AN:
1459780
Hom.:
0
Cov.:
29
AF XY:
0.00
AC XY:
0
AN XY:
726274
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:
9.01e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jun 18, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.61T>C (p.S21P) alteration is located in exon 2 (coding exon 2) of the CDH13 gene. This alteration results from a T to C substitution at nucleotide position 61, causing the serine (S) at amino acid position 21 to be replaced by a proline (P). 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
0.098
BayesDel_addAF
Benign
-0.014
T
BayesDel_noAF
Benign
-0.26
CADD
Benign
21
DANN
Uncertain
1.0
DEOGEN2
Benign
0.21
T;.;.;.;.;.
Eigen
Benign
0.18
Eigen_PC
Uncertain
0.32
FATHMM_MKL
Uncertain
0.84
D
LIST_S2
Benign
0.83
T;T;T;T;T;T
M_CAP
Benign
0.016
T
MetaRNN
Benign
0.28
T;T;T;T;T;T
MetaSVM
Benign
-0.98
T
MutationAssessor
Benign
0.55
N;.;N;N;N;.
PrimateAI
Benign
0.44
T
PROVEAN
Benign
-1.3
.;N;N;N;N;D
REVEL
Benign
0.19
Sift
Benign
0.045
.;D;T;T;T;T
Sift4G
Benign
0.26
T;T;T;T;T;T
Polyphen
0.79
P;.;.;.;.;.
Vest4
0.63
MutPred
0.63
Gain of sheet (P = 0.0827);.;Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);
MVP
0.81
MPC
0.27
ClinPred
0.66
D
GERP RS
6.0
Varity_R
0.22
gMVP
0.50

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: rs1001242904; hg19: chr16-82891982; API