rs771569331

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PP3_ModerateBP6

The NM_002354.3(EPCAM):c.518G>A(p.Arg173His) variant causes a missense change. The variant allele was found at a frequency of 0.0000633 in 1,610,616 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R173C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000064 ( 0 hom. )

Consequence

EPCAM
NM_002354.3 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:1

Conservation

PhyloP100: 5.00

Publications

1 publications found

Variant links:

COSMIC-nc: COSV109419894

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: Uncertain_significance. The variant received 1 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.937

BP6

Variant 2-47377040-G-A is Benign according to our data. Variant chr2-47377040-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 216559.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002354.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPCAM	NM_002354.3	MANE Select	c.518G>A	p.Arg173His	missense	Exon 5 of 9	NP_002345.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
EPCAM	ENST00000263735.9	TSL:1 MANE Select	c.518G>A	p.Arg173His	missense	Exon 5 of 9	ENSP00000263735.4
EPCAM	ENST00000405271.5	TSL:5	c.602G>A	p.Arg201His	missense	Exon 6 of 10	ENSP00000385476.1
EPCAM	ENST00000456133.5	TSL:5	n.602G>A		non_coding_transcript_exon	Exon 6 of 11	ENSP00000410675.1

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152034

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000656

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000830

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000637

AC:

AN:

251354

AF XY:

0.0000442

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000106

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000644

AC:

AN:

1458582

Hom.:

Cov.:

AF XY:

0.0000648

AC XY:

AN XY:

725864

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33420

American (AMR)

AF:

0.0000224

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26118

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39674

South Asian (SAS)

AF:

0.000104

AC:

AN:

86208

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53350

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.0000667

AC:

AN:

1109056

Other (OTH)

AF:

0.000116

AC:

AN:

60270

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.451

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0000526

AC:

AN:

152034

Hom.:

Cov.:

AF XY:

0.0000673

AC XY:

AN XY:

74250

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41374

American (AMR)

AF:

0.0000656

AC:

AN:

15252

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.000830

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10582

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68020

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.0000508

Hom.:

Bravo

AF:

0.0000642

ExAC

AF:

0.0000659

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000237

ClinVar

ClinVar submissions as Germline

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Congenital diarrhea 5 with tufting enteropathy (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.37

BayesDel_addAF

Uncertain

0.14

BayesDel_noAF

Pathogenic

0.18

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.36

Eigen

Uncertain

0.61

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.87

M_CAP

Uncertain

0.19

MetaRNN

Pathogenic

0.94

MetaSVM

Uncertain

0.34

MutationAssessor

Pathogenic

3.2

PhyloP100

5.0

PrimateAI

Benign

0.43

PROVEAN

Uncertain

-4.0

REVEL

Pathogenic

0.70

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.0020

Polyphen

1.0

Vest4

0.74

MVP

0.78

MPC

0.015

ClinPred

0.73

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.85

gMVP

0.59

Mutation Taster

=50/50

(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

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

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over