rs201645229

Positions:

• chr2-47373551-T-A
• chr2-47373551-T-C
• chr2-47373551-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1 PM2 BP4_Moderate

The NM_002354.3(EPCAM):​c.165T>A​(p.Asn55Lys) 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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: EPCAM NM_002354.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.366

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM1: In a chain Epithelial cell adhesion molecule (size 290) in uniprot entity EPCAM_HUMAN there are 12 pathogenic changes around while only 2 benign (86%) in NM_002354.3
• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.086897284).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPCAM	NM_002354.3	c.165T>A	p.Asn55Lys	missense_variant	2/9	ENST00000263735.9	NP_002345.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPCAM	ENST00000263735.9	c.165T>A	p.Asn55Lys	missense_variant	2/9	1	NM_002354.3	ENSP00000263735	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	9.4
DANN	Benign	0.95
DEOGEN2	Benign	0.026	T;T;.
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.73
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.63	.;T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.087	T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.5	.;M;.
MutationTaster	Benign	1.0	N;N
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-1.4	N;N;N
REVEL	Benign	0.020
Sift	Benign	0.33	T;T;T
Sift4G	Benign	0.30	T;T;T
Polyphen		0.45	P;B;.
Vest4		0.43
MutPred		0.32		Gain of ubiquitination at N83 (P = 0.0325);.;.;
MVP		0.34
MPC		0.015
ClinPred		0.16	T
GERP RS		2.5
Varity_R		0.087
gMVP		0.36

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-47600690;