Variant chr2-47377018-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000263735.9(EPCAM):c.496C>G(p.Leu166Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L166F) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Consequence

EPCAM
ENST00000263735.9 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0610

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 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPCAM	NM_002354.3 linkuse as main transcript	c.496C>G	p.Leu166Val	missense_variant	5/9	ENST00000263735.9	NP_002345.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
EPCAM	ENST00000263735.9 linkuse as main transcript	c.496C>G	p.Leu166Val	missense_variant	5/9	1	NM_002354.3	ENSP00000263735	P1
EPCAM	ENST00000405271.5 linkuse as main transcript	c.580C>G	p.Leu194Val	missense_variant	6/10	5		ENSP00000385476
EPCAM	ENST00000490733.1 linkuse as main transcript	n.345C>G		non_coding_transcript_exon_variant	3/6	3
EPCAM	ENST00000456133.5 linkuse as main transcript	c.580C>G	p.Leu194Val	missense_variant, NMD_transcript_variant	6/11	5		ENSP00000410675

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Uncertain

0.013

BayesDel_noAF

Benign

-0.22

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.036

T;T

Eigen

Benign

-0.53

Eigen_PC

Benign

-0.68

FATHMM_MKL

Benign

0.053

LIST_S2

Benign

0.60

.;T

M_CAP

Benign

0.024

MetaRNN

Benign

0.17

T;T

MetaSVM

Benign

-0.62

MutationAssessor

Uncertain

2.7

.;M

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.42

PROVEAN

Benign

-1.5

N;N

REVEL

Uncertain

0.42

Sift

Uncertain

0.0080

D;D

Sift4G

Uncertain

0.011

D;D

Polyphen

0.78

P;B

Vest4

0.42

MutPred

0.49

Loss of stability (P = 0.0837);.;

MVP

0.55

MPC

0.013

ClinPred

0.19

GERP RS

0.69

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.50

gMVP

0.34

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.28

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.28

Position offset: 1

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over