Variant rs2306907 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_001257.5(CDH13):c.782-4G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 1,609,752 control chromosomes in the GnomAD database, including 42,708 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.21 ( 3566 hom., cov: 32)

Exomes 𝑓: 0.23 ( 39142 hom. )

Consequence

CDH13
NM_001257.5 splice_region, intron

Scores

Splicing: ADA: 0.00001922

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.16

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 (BayesDel_noAF=-0.88).

BP6

Variant 16-83486473-G-A is Benign according to our data. Variant chr16-83486473-G-A is described in ClinVar as [Benign]. Clinvar id is 257650.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.277 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.782-4G>A		splice_region_variant, 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.782-4G>A		splice_region_variant, intron_variant		1	NM_001257.5	ENSP00000479395.1		P55290-1

Frequencies

GnomAD3 genomes

AF:

0.213

AC:

32424

AN:

151952

Hom.:

3565

Cov.:

show subpopulations

Gnomad AFR

AF:

0.154

Gnomad AMI

AF:

0.171

Gnomad AMR

AF:

0.284

Gnomad ASJ

AF:

0.233

Gnomad EAS

AF:

0.112

Gnomad SAS

AF:

0.147

Gnomad FIN

AF:

0.235

Gnomad MID

AF:

0.310

Gnomad NFE

AF:

0.240

Gnomad OTH

AF:

0.256

GnomAD3 exomes

AF:

0.229

AC:

56678

AN:

247390

Hom.:

7051

AF XY:

0.224

AC XY:

30012

AN XY:

134250

show subpopulations

Gnomad AFR exome

AF:

0.151

Gnomad AMR exome

AF:

0.333

Gnomad ASJ exome

AF:

0.235

Gnomad EAS exome

AF:

0.122

Gnomad SAS exome

AF:

0.150

Gnomad FIN exome

AF:

0.245

Gnomad NFE exome

AF:

0.242

Gnomad OTH exome

AF:

0.245

GnomAD4 exome

AF:

0.227

AC:

330603

AN:

1457682

Hom.:

39142

Cov.:

AF XY:

0.225

AC XY:

162797

AN XY:

724752

show subpopulations

Gnomad4 AFR exome

AF:

0.154

Gnomad4 AMR exome

AF:

0.331

Gnomad4 ASJ exome

AF:

0.236

Gnomad4 EAS exome

AF:

0.105

Gnomad4 SAS exome

AF:

0.146

Gnomad4 FIN exome

AF:

0.243

Gnomad4 NFE exome

AF:

0.235

Gnomad4 OTH exome

AF:

0.216

GnomAD4 genome

AF:

0.213

AC:

32436

AN:

152070

Hom.:

3566

Cov.:

AF XY:

0.213

AC XY:

15829

AN XY:

74294

show subpopulations

Gnomad4 AFR

AF:

0.154

Gnomad4 AMR

AF:

0.284

Gnomad4 ASJ

AF:

0.233

Gnomad4 EAS

AF:

0.111

Gnomad4 SAS

AF:

0.147

Gnomad4 FIN

AF:

0.235

Gnomad4 NFE

AF:

0.240

Gnomad4 OTH

AF:

0.257

Alfa

AF:

0.236

Hom.:

7371

Bravo

AF:

0.219

EpiCase

AF:

0.254

EpiControl

AF:

0.245

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 09, 2021	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.031

DANN

Benign

0.71

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000019

dbscSNV1_RF

Benign

0.0020

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.

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