rs17715450

Positions:

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_001793.6(CDH3):c.2239C>A(p.Arg747=) 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:7

Conservation

PhyloP100: 5.74

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 93783.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-68695882-C-A is described in Lovd as [Benign].

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/exons	MANE	UniProt
CDH3	NM_001793.6 linkuse as main transcript	c.2239C>A	p.Arg747=	synonymous_variant	15/16	ENST00000264012.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDH3	ENST00000264012.9 linkuse as main transcript	c.2239C>A	p.Arg747=	synonymous_variant	15/16	1	NM_001793.6	P1	P22223-1

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

GnomAD3 exomes

AF:

0.533

AC:

133886

AN:

251290

Hom.:

36494

AF XY:

0.541

AC XY:

73533

AN XY:

135852

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 SAS exome

AF:

0.540

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

Gnomad4 AFR exome

AF:

0.297

Gnomad4 AMR exome

AF:

0.450

Gnomad4 ASJ exome

AF:

0.554

Gnomad4 EAS exome

AF:

0.553

Gnomad4 SAS exome

AF:

0.537

Gnomad4 FIN exome

AF:

0.598

Gnomad4 NFE exome

AF:

0.591

Gnomad4 OTH exome

AF:

0.553

GnomAD4 genome

AF:

0.499

AC:

75758

AN:

151956

Hom.:

20056

Cov.:

AF XY:

0.498

AC XY:

36953

AN XY:

74250

show subpopulations

Gnomad4 AFR

AF:

0.311

Gnomad4 AMR

AF:

0.477

Gnomad4 ASJ

AF:

0.546

Gnomad4 EAS

AF:

0.500

Gnomad4 SAS

AF:

0.540

Gnomad4 FIN

AF:

0.597

Gnomad4 NFE

AF:

0.594

Gnomad4 OTH

AF:

0.510

Alfa

AF:

0.562

Hom.:

47454

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:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

EEM syndrome

Benign:3

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 14, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Mendelics	May 28, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	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:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 26, 2018	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. -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Oct 02, 2013

- -

Congenital hypotrichosis with juvenile macular dystrophy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Uncertain

-0.040

CADD

Benign

DANN

Benign

0.71

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

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