rs17715450

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_001793.6(CDH3):c.2239C>A(p.Arg747Arg) variant causes a synonymous change. The variant allele was found at a frequency of 0.566 in 1,613,546 control chromosomes in the GnomAD database, including 262,681 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.50 ( 20056 hom., cov: 31)

Exomes 𝑓: 0.57 ( 242625 hom. )

Consequence

CDH3
NM_001793.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 5.74

Publications

35 publications found

Variant links:

Genes affected

CDH3 (HGNC:1762): (cadherin 3) This gene encodes a classical cadherin of the cadherin superfamily. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed to generate the mature glycoprotein. This calcium-dependent cell-cell adhesion protein is comprised of five extracellular cadherin repeats, a transmembrane region and a highly conserved cytoplasmic tail. This gene is located in a gene cluster in a region on the long arm of chromosome 16 that is involved in loss of heterozygosity events in breast and prostate cancer. In addition, aberrant expression of this protein is observed in cervical adenocarcinomas. Mutations in this gene are associated with hypotrichosis with juvenile macular dystrophy and ectodermal dysplasia, ectrodactyly, and macular dystrophy syndrome (EEMS). [provided by RefSeq, Nov 2015]

CDH3 Gene-Disease associations (from GenCC):

EEM syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, ClinGen, Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics
congenital hypotrichosis with juvenile macular dystrophy
Inheritance: AR Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Orphanet, G2P, Labcorp Genetics (formerly Invitae)

CDH3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP6

Variant 16-68695882-C-A is Benign according to our data. Variant chr16-68695882-C-A is described in ClinVar as Benign. ClinVar VariationId is 93783.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.589 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH3	NM_001793.6 link	c.2239C>A	p.Arg747Arg	synonymous_variant	Exon 15 of 16	ENST00000264012.9	NP_001784.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDH3	ENST00000264012.9 link	c.2239C>A	p.Arg747Arg	synonymous_variant	Exon 15 of 16	1	NM_001793.6	ENSP00000264012.4

Frequencies

GnomAD3 genomes

AF:

0.499

AC:

75739

AN:

151838

Hom.:

20056

Cov.:

show subpopulations

Gnomad AFR

AF:

0.312

Gnomad AMI

AF:

0.688

Gnomad AMR

AF:

0.477

Gnomad ASJ

AF:

0.546

Gnomad EAS

AF:

0.500

Gnomad SAS

AF:

0.540

Gnomad FIN

AF:

0.597

Gnomad MID

AF:

0.579

Gnomad NFE

AF:

0.594

Gnomad OTH

AF:

0.510

GnomAD2 exomes

AF:

0.533

AC:

133886

AN:

251290

AF XY:

0.541

show subpopulations

Gnomad AFR exome

AF:

0.308

Gnomad AMR exome

AF:

0.441

Gnomad ASJ exome

AF:

0.552

Gnomad EAS exome

AF:

0.484

Gnomad FIN exome

AF:

0.591

Gnomad NFE exome

AF:

0.585

Gnomad OTH exome

AF:

0.551

GnomAD4 exome

AF:

0.573

AC:

837586

AN:

1461590

Hom.:

242625

Cov.:

AF XY:

0.573

AC XY:

416511

AN XY:

727110

show subpopulations

African (AFR)

AF:

0.297

AC:

9930

AN:

33478

American (AMR)

AF:

0.450

AC:

20116

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.554

AC:

14468

AN:

26136

East Asian (EAS)

AF:

0.553

AC:

21943

AN:

39688

South Asian (SAS)

AF:

0.537

AC:

46352

AN:

86258

European-Finnish (FIN)

AF:

0.598

AC:

31950

AN:

53390

Middle Eastern (MID)

AF:

0.510

AC:

2939

AN:

5768

European-Non Finnish (NFE)

AF:

0.591

AC:

656515

AN:

1111770

Other (OTH)

AF:

0.553

AC:

33373

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

21659

43317

64976

86634

108293

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17886

35772

53658

71544

89430

<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:

0.499

AC:

75758

AN:

151956

Hom.:

20056

Cov.:

AF XY:

0.498

AC XY:

36953

AN XY:

74250

show subpopulations

African (AFR)

AF:

0.311

AC:

12893

AN:

41436

American (AMR)

AF:

0.477

AC:

7287

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.546

AC:

1895

AN:

3470

East Asian (EAS)

AF:

0.500

AC:

2574

AN:

5152

South Asian (SAS)

AF:

0.540

AC:

2591

AN:

4802

European-Finnish (FIN)

AF:

0.597

AC:

6303

AN:

10560

Middle Eastern (MID)

AF:

0.571

AC:

168

AN:

294

European-Non Finnish (NFE)

AF:

0.594

AC:

40345

AN:

67956

Other (OTH)

AF:

0.510

AC:

1076

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1834

3669

5503

7338

9172

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

678

1356

2034

2712

3390

<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:

0.547

Hom.:

74729

Bravo

AF:

0.480

Asia WGS

AF:

0.472

AC:

1643

AN:

3478

EpiCase

AF:

0.583

EpiControl

AF:

0.582

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

EEM syndrome

Benign:3

May 28, 2019

Mendelics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Apr 26, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

Oct 02, 2013

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Congenital hypotrichosis with juvenile macular dystrophy

Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Uncertain

-0.040

CADD

Benign

(source)

DANN

Benign

0.71

PhyloP100

5.7

PromoterAI

-0.027

Neutral

(source)

Mutation Taster

=61/39

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