2-47369508-G-C

Position:

• chr2-47369508-G-C

Variant summary

Our verdict is Pathogenic. Variant got 13 ACMG points: 13P and 0B. PVS1 PS1_Moderate PM2 PP5

The NM_002354.3(EPCAM):​c.3G>C​(p.Met1?) variant causes a start lost 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 ClinVar as Pathogenic (no stars).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: EPCAM NM_002354.3 start_lost
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 2.41

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 Pathogenic. Variant got 13 ACMG points.

• PVS1: Start lost variant, no new inframe start found.
• PS1: Another start lost variant in NM_002354.3 (EPCAM) was described as [Likely_pathogenic] in ClinVar as 1801655
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 2-47369508-G-C is Pathogenic according to our data. Variant chr2-47369508-G-C is described in ClinVar as [Pathogenic]. Clinvar id is 1801668.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EPCAM	NM_002354.3	c.3G>C	p.Met1?	start_lost	1/9	ENST00000263735.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EPCAM	ENST00000263735.9	c.3G>C	p.Met1?	start_lost	1/9	1	NM_002354.3	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1399242 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 691694

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Gastric cancer Pathogenic:1

Pathogenic, no assertion criteria provided

research

Laboratory for Genotyping Development, RIKEN

Jul 01, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.62	D
BayesDel_noAF	Pathogenic	0.29
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.20	T;.
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Benign	0.75	D
LIST_S2	Uncertain	0.90	D;D
M_CAP	Pathogenic	0.99	D
MetaRNN	Pathogenic	0.99	D;D
MetaSVM	Uncertain	0.16	D
MutationTaster	Benign	1.0	D;D
PROVEAN	Benign	-1.4	N;N
REVEL	Uncertain	0.59
Sift	Pathogenic	0.0	D;D
Sift4G	Uncertain	0.049	D;D
Polyphen		0.92	P;.
Vest4		0.84
MutPred		1.0		Loss of glycosylation at P3 (P = 0.04);Loss of glycosylation at P3 (P = 0.04);
MVP		0.73
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		0.52

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: chr2-47596647;