chr2-47386560-T-C

Variant names:

Variant summary

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

The NM_002354.3(EPCAM):c.904-12T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0389 in 1,591,436 control chromosomes in the GnomAD database, including 1,405 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.034 ( 124 hom., cov: 33)

Exomes 𝑓: 0.039 ( 1281 hom. )

Consequence

EPCAM
NM_002354.3 intron

Scores

Splicing: ADA: 0.00009840

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -1.60

Publications

3 publications found

Variant links:

Genes affected

EPCAM (HGNC:11529): (epithelial cell adhesion molecule) This gene encodes a carcinoma-associated antigen and is a member of a family that includes at least two type I membrane proteins. This antigen is expressed on most normal epithelial cells and gastrointestinal carcinomas and functions as a homotypic calcium-independent cell adhesion molecule. The antigen is being used as a target for immunotherapy treatment of human carcinomas. Mutations in this gene result in congenital tufting enteropathy. [provided by RefSeq, Dec 2008]

EPCAM Gene-Disease associations (from GenCC):

Lynch syndrome
Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
Lynch syndrome 8
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, G2P, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
congenital diarrhea 5 with tufting enteropathy
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, Orphanet, G2P, Ambry Genetics
hereditary breast carcinoma
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

EPCAM 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 (BayesDel_noAF=-0.78).

BP6

Variant 2-47386560-T-C is Benign according to our data. Variant chr2-47386560-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 258645.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0584 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPCAM	NM_002354.3 link	c.904-12T>C		intron_variant	Intron 8 of 8	ENST00000263735.9	NP_002345.2	P16422

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
EPCAM	ENST00000263735.9 link	c.904-12T>C	intron_variant	Intron 8 of 8	1	NM_002354.3	ENSP00000263735.4	P16422
EPCAM	ENST00000405271.5 link	c.988-12T>C	intron_variant	Intron 9 of 9	5		ENSP00000385476.1	B5MCA4
EPCAM	ENST00000456133.5 link	n.988-12T>C	intron_variant	Intron 9 of 10	5		ENSP00000410675.1	B5MCA4

Frequencies

GnomAD3 genomes

AF:

0.0343

AC:

5221

AN:

152190

Hom.:

123

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00825

Gnomad AMI

AF:

0.0395

Gnomad AMR

AF:

0.0617

Gnomad ASJ

AF:

0.0378

Gnomad EAS

AF:

0.000576

Gnomad SAS

AF:

0.0566

Gnomad FIN

AF:

0.0458

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0430

Gnomad OTH

AF:

0.0363

GnomAD2 exomes

AF:

0.0402

AC:

9992

AN:

248810

AF XY:

0.0411

show subpopulations

Gnomad AFR exome

AF:

0.00627

Gnomad AMR exome

AF:

0.0561

Gnomad ASJ exome

AF:

0.0419

Gnomad EAS exome

AF:

0.000437

Gnomad FIN exome

AF:

0.0467

Gnomad NFE exome

AF:

0.0391

Gnomad OTH exome

AF:

0.0392

GnomAD4 exome

AF:

0.0394

AC:

56676

AN:

1439128

Hom.:

1281

Cov.:

AF XY:

0.0403

AC XY:

28826

AN XY:

716108

show subpopulations

African (AFR)

AF:

0.00530

AC:

176

AN:

33192

American (AMR)

AF:

0.0548

AC:

2422

AN:

44182

Ashkenazi Jewish (ASJ)

AF:

0.0399

AC:

1030

AN:

25840

East Asian (EAS)

AF:

0.000228

AC:

AN:

39488

South Asian (SAS)

AF:

0.0648

AC:

5361

AN:

82742

European-Finnish (FIN)

AF:

0.0445

AC:

2355

AN:

52962

Middle Eastern (MID)

AF:

0.0387

AC:

213

AN:

5508

European-Non Finnish (NFE)

AF:

0.0391

AC:

42866

AN:

1095638

Other (OTH)

AF:

0.0377

AC:

2244

AN:

59576

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.444

Heterozygous variant carriers

2174

4348

6522

8696

10870

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1588

3176

4764

6352

7940

<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:

0.0343

AC:

5222

AN:

152308

Hom.:

124

Cov.:

AF XY:

0.0361

AC XY:

2686

AN XY:

74484

show subpopulations

African (AFR)

AF:

0.00823

AC:

342

AN:

41568

American (AMR)

AF:

0.0616

AC:

942

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.0378

AC:

131

AN:

3468

East Asian (EAS)

AF:

0.000578

AC:

AN:

5192

South Asian (SAS)

AF:

0.0570

AC:

275

AN:

4822

European-Finnish (FIN)

AF:

0.0458

AC:

486

AN:

10620

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0430

AC:

2927

AN:

68036

Other (OTH)

AF:

0.0360

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

260

521

781

1042

1302

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

132

198

264

330

<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:

0.0398

Hom.:

Bravo

AF:

0.0318

Asia WGS

AF:

0.0220

AC:

AN:

3472

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Mar 04, 2025

Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Lynch syndrome 8

Benign:1

Jul 07, 2023

KCCC/NGS Laboratory, Kuwait Cancer Control Center

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

Benign

-0.78

CADD

Benign

2.6

(source)

DANN

Benign

0.81

PhyloP100

-1.6

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000098

dbscSNV1_RF

Benign

0.0

SpliceAI score (max)

0.040

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