rs2276330

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP2BA1

This summary comes from the ClinGen Evidence Repository: The NM_004360.5(CDH1):c.1937-13T>C variant has an allele frequency of 0.16607 (16.6%, 4107/24730 alleles, 330 homozygotes) in the European (Finnish) subpopulation of the gnomAD v2.1.1 cohort (BA1; BP2). Therefore, this variant meets criteria to be classified as benign. ACMG/AMP criteria applied, as specified by the CDH1 Variant Curation Expert Panel (Variant Interpretation Guidelines Version 3.1): BA1, BP2. LINK:https://erepo.genome.network/evrepo/ui/classification/CA163616/MONDO:0007648/007

Frequency

Genomes: 𝑓 0.095 ( 871 hom., cov: 31)

Exomes 𝑓: 0.12 ( 11676 hom. )

Consequence

CDH1
NM_004360.5 intron

Scores

Clinical Significance

Benign reviewed by expert panel U:1B:16

Conservation

PhyloP100: 0.184

Publications

30 publications found

Variant links:

Genes affected

CDH1 (HGNC:1748): (cadherin 1) 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. Mutations in this gene are correlated with gastric, breast, colorectal, thyroid and ovarian cancer. Loss of function of this gene is thought to contribute to cancer progression by increasing proliferation, invasion, and/or metastasis. The ectodomain of this protein mediates bacterial adhesion to mammalian cells and the cytoplasmic domain is required for internalization. This gene is present in a gene cluster with other members of the cadherin family on chromosome 16. [provided by RefSeq, Nov 2015]

CDH1 Gene-Disease associations (from GenCC):

blepharocheilodontic syndrome 1
Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P, Illumina
CDH1-related diffuse gastric and lobular breast cancer syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), G2P
hereditary breast carcinoma
Inheritance: AD Classification: DEFINITIVE Submitted by: Ambry Genetics
hereditary diffuse gastric adenocarcinoma
Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics
cleft soft palate
Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
orofacial cleft 3
Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
blepharocheilodontic syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
familial ovarian cancer
Inheritance: Unknown Classification: NO_KNOWN Submitted by: ClinGen

CDH1 links:

ENSG00000260798 (HGNC:):

ENSG00000260798 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP2

For more information check the summary or visit ClinGen Evidence Repository.

BA1

For more information check the summary or visit ClinGen Evidence Repository.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004360.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CDH1	NM_004360.5	MANE Select	c.1937-13T>C	intron	N/A	NP_004351.1	A0A0U2ZQU7
CDH1	NM_001317184.2		c.1754-13T>C	intron	N/A	NP_001304113.1	P12830-2
CDH1	NM_001317185.2		c.389-13T>C	intron	N/A	NP_001304114.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CDH1	ENST00000261769.10	TSL:1 MANE Select	c.1937-13T>C	intron	N/A	ENSP00000261769.4	P12830-1
CDH1	ENST00000422392.6	TSL:1	c.1754-13T>C	intron	N/A	ENSP00000414946.2	P12830-2
CDH1	ENST00000562836.5	TSL:1	n.2008-13T>C	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0949

AC:

14433

AN:

152152

Hom.:

872

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0243

Gnomad AMI

AF:

0.0877

Gnomad AMR

AF:

0.0666

Gnomad ASJ

AF:

0.132

Gnomad EAS

AF:

0.0705

Gnomad SAS

AF:

0.0536

Gnomad FIN

AF:

0.159

Gnomad MID

AF:

0.111

Gnomad NFE

AF:

0.137

Gnomad OTH

AF:

0.0920

GnomAD2 exomes

AF:

0.103

AC:

25875

AN:

250252

AF XY:

0.105

show subpopulations

Gnomad AFR exome

AF:

0.0211

Gnomad AMR exome

AF:

0.0476

Gnomad ASJ exome

AF:

0.121

Gnomad EAS exome

AF:

0.0795

Gnomad FIN exome

AF:

0.165

Gnomad NFE exome

AF:

0.136

Gnomad OTH exome

AF:

0.111

GnomAD4 exome

AF:

0.122

AC:

173911

AN:

1429786

Hom.:

11676

Cov.:

AF XY:

0.120

AC XY:

85559

AN XY:

713624

show subpopulations

African (AFR)

AF:

0.0225

AC:

739

AN:

32806

American (AMR)

AF:

0.0497

AC:

2222

AN:

44676

Ashkenazi Jewish (ASJ)

AF:

0.127

AC:

3283

AN:

25918

East Asian (EAS)

AF:

0.0544

AC:

2150

AN:

39514

South Asian (SAS)

AF:

0.0543

AC:

4650

AN:

85578

European-Finnish (FIN)

AF:

0.169

AC:

8986

AN:

53066

Middle Eastern (MID)

AF:

0.0854

AC:

473

AN:

5540

European-Non Finnish (NFE)

AF:

0.133

AC:

144550

AN:

1083378

Other (OTH)

AF:

0.116

AC:

6858

AN:

59310

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

7629

15259

22888

30518

38147

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4922

9844

14766

19688

24610

<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:

0.0948

AC:

14431

AN:

152270

Hom.:

871

Cov.:

AF XY:

0.0932

AC XY:

6938

AN XY:

74444

show subpopulations

African (AFR)

AF:

0.0243

AC:

1009

AN:

41580

American (AMR)

AF:

0.0665

AC:

1017

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.132

AC:

457

AN:

3472

East Asian (EAS)

AF:

0.0709

AC:

367

AN:

5178

South Asian (SAS)

AF:

0.0536

AC:

259

AN:

4828

European-Finnish (FIN)

AF:

0.159

AC:

1684

AN:

10594

Middle Eastern (MID)

AF:

0.112

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.137

AC:

9332

AN:

68006

Other (OTH)

AF:

0.0915

AC:

193

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

659

1318

1977

2636

3295

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

164

328

492

656

820

<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:

0.115

Hom.:

2225

Bravo

AF:

0.0869

Asia WGS

AF:

0.0500

AC:

174

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:reviewed by expert panel

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (5)

Hereditary diffuse gastric adenocarcinoma (4)

Hereditary cancer-predisposing syndrome (3)

not provided (3)

CDH1-related diffuse gastric and lobular breast cancer syndrome (1)

Prostate cancer (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

9.0

(source)

DANN

Benign

0.60

PhyloP100

0.18

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

Splicevardb

3.0

SpliceAI score (max)

0.10

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over