rs72807847

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001257.5(CDH13):c.116A>G(p.Asn39Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0142 in 1,613,538 control chromosomes in the GnomAD database, including 532 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.019 ( 53 hom., cov: 33)

Exomes 𝑓: 0.014 ( 479 hom. )

Consequence

CDH13
NM_001257.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.55

Publications

15 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0023998022).

BP6

Variant 16-82858432-A-G is Benign according to our data. Variant chr16-82858432-A-G is described in ClinVar as Benign. ClinVar VariationId is 257648.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.074 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH13	NM_001257.5 link	c.116A>G	p.Asn39Ser	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
CDH13	ENST00000567109.6 link	c.116A>G	p.Asn39Ser	missense_variant	Exon 2 of 14	1	NM_001257.5	ENSP00000479395.1		P55290-1

Frequencies

GnomAD3 genomes

AF:

0.0190

AC:

2895

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0334

Gnomad AMI

AF:

0.0592

Gnomad AMR

AF:

0.00720

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.0487

Gnomad SAS

AF:

0.0808

Gnomad FIN

AF:

0.00668

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00886

Gnomad OTH

AF:

0.0120

GnomAD2 exomes

AF:

0.0214

AC:

5328

AN:

249040

AF XY:

0.0240

show subpopulations

Gnomad AFR exome

AF:

0.0352

Gnomad AMR exome

AF:

0.00440

Gnomad ASJ exome

AF:

0.000796

Gnomad EAS exome

AF:

0.0532

Gnomad FIN exome

AF:

0.00548

Gnomad NFE exome

AF:

0.00870

Gnomad OTH exome

AF:

0.0151

GnomAD4 exome

AF:

0.0137

AC:

19985

AN:

1461196

Hom.:

479

Cov.:

AF XY:

0.0156

AC XY:

11364

AN XY:

726908

show subpopulations

African (AFR)

AF:

0.0356

AC:

1191

AN:

33472

American (AMR)

AF:

0.00438

AC:

196

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.000765

AC:

AN:

26130

East Asian (EAS)

AF:

0.0374

AC:

1483

AN:

39698

South Asian (SAS)

AF:

0.0772

AC:

6656

AN:

86204

European-Finnish (FIN)

AF:

0.00590

AC:

315

AN:

53398

Middle Eastern (MID)

AF:

0.0161

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00814

AC:

9051

AN:

1111444

Other (OTH)

AF:

0.0162

AC:

980

AN:

60360

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

918

1836

2753

3671

4589

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

426

852

1278

1704

2130

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0190

AC:

2900

AN:

152342

Hom.:

Cov.:

AF XY:

0.0205

AC XY:

1526

AN XY:

74494

show subpopulations

African (AFR)

AF:

0.0333

AC:

1386

AN:

41572

American (AMR)

AF:

0.00712

AC:

109

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00115

AC:

AN:

3472

East Asian (EAS)

AF:

0.0484

AC:

251

AN:

5186

South Asian (SAS)

AF:

0.0806

AC:

389

AN:

4824

European-Finnish (FIN)

AF:

0.00668

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00886

AC:

603

AN:

68036

Other (OTH)

AF:

0.0152

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

142

284

427

569

711

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

160

200

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0128

Hom.:

Bravo

AF:

0.0180

TwinsUK

AF:

0.00944

AC:

ALSPAC

AF:

0.00830

AC:

ESP6500AA

AF:

0.0312

AC:

118

ESP6500EA

AF:

0.00742

AC:

ExAC

AF:

0.0224

AC:

2710

Asia WGS

AF:

0.0640

AC:

222

AN:

3478

EpiCase

AF:

0.00873

EpiControl

AF:

0.00705

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jun 10, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 27238071, 25450229) -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.063

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.70

CADD

Benign

(source)

DANN

Benign

0.59

DEOGEN2

Benign

0.048

T;.;.;.;.;.

Eigen

Benign

-0.89

Eigen_PC

Benign

-0.75

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.75

T;T;T;T;T;T

MetaRNN

Benign

0.0024

T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

N;.;N;N;N;.

PhyloP100

2.6

PrimateAI

Benign

0.22

PROVEAN

Benign

-0.060

.;N;N;N;N;D

REVEL

Benign

0.11

Sift

Benign

0.78

.;T;T;T;T;T

Sift4G

Benign

0.73

T;T;T;T;T;T

Polyphen

0.0

B;.;.;.;.;.

Vest4

0.18

MPC

0.059

ClinPred

0.00015

GERP RS

3.6

Varity_R

0.034

gMVP

0.098

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over