chr16-82858467-C-G

Variant summary

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

The NM_001257.5(CDH13):ā€‹c.151C>Gā€‹(p.Leu51Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000696 in 1,436,446 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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‘“: 7.0e-7 ( 0 hom. )

Consequence

CDH13
NM_001257.5 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.35
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]

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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=0.23945063).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CDH13NM_001257.5 linkuse as main transcriptc.151C>G p.Leu51Val missense_variant 2/14 ENST00000567109.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CDH13ENST00000567109.6 linkuse as main transcriptc.151C>G p.Leu51Val missense_variant 2/141 NM_001257.5 P1P55290-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.96e-7
AC:
1
AN:
1436446
Hom.:
0
Cov.:
26
AF XY:
0.00
AC XY:
0
AN XY:
716166
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:
9.18e-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
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJun 18, 2021The c.151C>G (p.L51V) alteration is located in exon 2 (coding exon 2) of the CDH13 gene. This alteration results from a C to G substitution at nucleotide position 151, causing the leucine (L) at amino acid position 51 to be replaced by a valine (V). 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
0.074
BayesDel_addAF
Benign
-0.062
T
BayesDel_noAF
Benign
-0.33
CADD
Benign
20
DANN
Uncertain
1.0
DEOGEN2
Benign
0.086
T;.;.;.;.;.
Eigen
Benign
-0.00019
Eigen_PC
Benign
0.14
FATHMM_MKL
Uncertain
0.83
D
LIST_S2
Uncertain
0.88
D;D;D;D;D;T
M_CAP
Benign
0.016
T
MetaRNN
Benign
0.24
T;T;T;T;T;T
MetaSVM
Benign
-0.92
T
MutationAssessor
Benign
2.0
M;.;M;M;M;.
MutationTaster
Benign
0.61
N;N;N;N;N;N;N
PrimateAI
Benign
0.48
T
PROVEAN
Benign
-1.0
.;N;N;N;N;D
REVEL
Benign
0.084
Sift
Benign
0.048
.;D;D;D;D;D
Sift4G
Benign
0.24
T;T;D;D;T;D
Polyphen
0.010
B;.;.;.;.;.
Vest4
0.42
MutPred
0.55
Gain of catalytic residue at L51 (P = 0.0617);.;Gain of catalytic residue at L51 (P = 0.0617);Gain of catalytic residue at L51 (P = 0.0617);Gain of catalytic residue at L51 (P = 0.0617);Gain of catalytic residue at L51 (P = 0.0617);
MVP
0.79
MPC
0.081
ClinPred
0.28
T
GERP RS
4.1
Varity_R
0.14
gMVP
0.32

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-82892072; API