chr2-47369525-T-C

Position:

• chr2-47369525-T-C

Variant summary

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

The NM_002354.3(EPCAM):​c.20T>C​(p.Leu7Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: EPCAM NM_002354.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.578

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 (HGNC:):

ACMG classification

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	c.20T>C	p.Leu7Pro	missense_variant	1/9	ENST00000263735.9	NP_002345.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPCAM	ENST00000263735.9	c.20T>C	p.Leu7Pro	missense_variant	1/9	1	NM_002354.3	ENSP00000263735.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1420054 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 703608

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

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.030
CADD	Benign	23
DANN	Benign	0.63
DEOGEN2	Benign	0.12	T;.
Eigen	Benign	-0.86
Eigen_PC	Benign	-0.90
FATHMM_MKL	Benign	0.062	N
LIST_S2	Benign	0.36	T;T
M_CAP	Pathogenic	0.82	D
MetaRNN	Uncertain	0.46	T;T
MetaSVM	Benign	-0.39	T
MutationAssessor	Benign	1.8	L;.
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-1.2	N;N
REVEL	Uncertain	0.47
Sift	Uncertain	0.0030	D;D
Sift4G	Uncertain	0.0050	D;D
Polyphen		0.024	B;.
Vest4		0.53
MutPred		0.67		Gain of loop (P = 0.0013);Gain of loop (P = 0.0013);
MVP		0.30
MPC		0.039
ClinPred		0.58	D
GERP RS		1.3
Varity_R		0.39
gMVP		0.74

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: chr2-47596664;