NM_002354.3:c.1A>C

Variant names:

• chr2-47369506-A-C
• NM_002354.3:c.1A>C

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PVS1_Strong PM2 PP5

The NM_002354.3(EPCAM):​c.1A>C​(p.Met1?) variant causes a initiator codon change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in Lovd as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: EPCAM NM_002354.3 initiator_codon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.31

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 Likely_pathogenic. Variant got 7 ACMG points.

• PVS1: Start lost variant, next in-frame start position is after 6 pathogenic variants. Next in-frame start position is after 69 codons. Genomic position: 47373828. Lost 0.217 part of the original CDS.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 2-47369506-A-C is Pathogenic according to our data. Variant chr2-47369506-A-C is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPCAM	NM_002354.3	c.1A>C	p.Met1?	initiator_codon_variant	Exon 1 of 9	ENST00000263735.9	NP_002345.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPCAM	ENST00000263735.9	c.1A>C	p.Met1?	initiator_codon_variant	Exon 1 of 9	1	NM_002354.3	ENSP00000263735.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.36	D
BayesDel_noAF	Pathogenic	0.28
CADD	Benign	18
DANN	Benign	0.86
DEOGEN2	Benign	0.16	T;.
Eigen	Benign	0.17
Eigen_PC	Benign	0.16
FATHMM_MKL	Benign	0.55	D
LIST_S2	Uncertain	0.90	D;D
M_CAP	Pathogenic	1.0	D
MetaRNN	Pathogenic	0.99	D;D
MetaSVM	Uncertain	-0.031	T
PROVEAN	Benign	-1.1	N;N
REVEL	Uncertain	0.55
Sift	Pathogenic	0.0	D;D
Sift4G	Benign	0.44	T;D
Polyphen		0.70	P;.
Vest4		0.87
MutPred		1.0		Loss of glycosylation at P3 (P = 0.1062);Loss of glycosylation at P3 (P = 0.1062);
MVP		0.76
ClinPred		1.0	D
GERP RS		4.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.96
gMVP		0.44

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: chr2-47596645;