Variant 16-82639442-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001220488.2(CDH13):c.163C>T(p.Pro55Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.99 in 1,535,282 control chromosomes in the GnomAD database, including 753,368 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.95 ( 68789 hom., cov: 32)

Exomes 𝑓: 0.99 ( 684579 hom. )

Consequence

CDH13
NM_001220488.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.187

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]

CDH13 links:

CDH13 (HGNC:):

CDH13 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.2290827E-6).

BP6

Variant 16-82639442-C-T is Benign according to our data. Variant chr16-82639442-C-T is described in ClinVar as [Benign]. Clinvar id is 257644.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDH13	NM_001257.5 linkuse as main transcript	c.45+12305C>T		intron_variant		ENST00000567109.6	NP_001248.1	P55290-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDH13	ENST00000567109.6 linkuse as main transcript	c.45+12305C>T		intron_variant		1	NM_001257.5	ENSP00000479395.1		P55290-1

Frequencies

GnomAD3 genomes

AF:

0.947

AC:

144095

AN:

152146

Hom.:

68735

Cov.:

show subpopulations

Gnomad AFR

AF:

0.818

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.976

Gnomad ASJ

AF:

0.997

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

1.00

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

0.994

Gnomad NFE

AF:

0.999

Gnomad OTH

AF:

0.956

GnomAD3 exomes

AF:

0.989

AC:

126958

AN:

128384

Hom.:

62857

AF XY:

0.991

AC XY:

69664

AN XY:

70308

show subpopulations

Gnomad AFR exome

AF:

0.823

Gnomad AMR exome

AF:

0.990

Gnomad ASJ exome

AF:

0.996

Gnomad EAS exome

AF:

1.00

Gnomad SAS exome

AF:

0.999

Gnomad FIN exome

AF:

1.00

Gnomad NFE exome

AF:

0.999

Gnomad OTH exome

AF:

0.993

GnomAD4 exome

AF:

0.995

AC:

1375544

AN:

1383018

Hom.:

684579

Cov.:

AF XY:

0.995

AC XY:

679149

AN XY:

682434

show subpopulations

Gnomad4 AFR exome

AF:

0.819

Gnomad4 AMR exome

AF:

0.989

Gnomad4 ASJ exome

AF:

0.996

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

1.00

Gnomad4 FIN exome

AF:

1.00

Gnomad4 NFE exome

AF:

1.00

Gnomad4 OTH exome

AF:

0.988

GnomAD4 genome

AF:

0.947

AC:

144209

AN:

152264

Hom.:

68789

Cov.:

AF XY:

0.949

AC XY:

70650

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.819

Gnomad4 AMR

AF:

0.976

Gnomad4 ASJ

AF:

0.997

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

1.00

Gnomad4 FIN

AF:

1.00

Gnomad4 NFE

AF:

0.999

Gnomad4 OTH

AF:

0.956

Alfa

AF:

0.996

Hom.:

85178

Bravo

AF:

0.938

TwinsUK

AF:

1.00

AC:

3707

ALSPAC

AF:

1.00

AC:

3853

ExAC

AF:

0.982

AC:

13630

Asia WGS

AF:

0.992

AC:

3452

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.61

CADD

Benign

3.8

DANN

Benign

0.37

Eigen

Benign

-0.78

Eigen_PC

Benign

-0.94

FATHMM_MKL

Benign

0.00081

LIST_S2

Benign

0.24

MetaRNN

Benign

0.0000012

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.20

REVEL

Benign

0.022

Sift

Benign

0.95

Vest4

0.017

MPC

0.073

ClinPred

0.0027

GERP RS

2.2

gMVP

0.077

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over