chr2-47385159-C-T

Position:

• chr2-47385159-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002354.3(EPCAM):​c.859-7C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00391 in 1,609,448 control chromosomes in the GnomAD database, including 243 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.021 (132 hom., cov: 33)
  • Exomes 𝑓: 0.0021 (111 hom.)
• Consequence: EPCAM NM_002354.3 splice_region, intron
• Scores: Splicing: ADA: 0.00004457
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: -0.311

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 Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP6: Variant 2-47385159-C-T is Benign according to our data. Variant chr2-47385159-C-T is described in ClinVar as [Benign]. Clinvar id is 258644.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-47385159-C-T is described in Lovd as [Likely_benign]. Variant chr2-47385159-C-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0716 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPCAM	NM_002354.3	c.859-7C>T		splice_region_variant, intron_variant		ENST00000263735.9	NP_002345.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPCAM	ENST00000263735.9	c.859-7C>T		splice_region_variant, intron_variant		1	NM_002354.3	ENSP00000263735.4
EPCAM	ENST00000405271.5	c.943-7C>T		splice_region_variant, intron_variant		5		ENSP00000385476.1
EPCAM	ENST00000456133.5	n.943-7C>T		splice_region_variant, intron_variant		5		ENSP00000410675.1
EPCAM	ENST00000490733.1	n.708-7C>T		splice_region_variant, intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.0210 AC: 3194 AN: 151980 Hom.: 132 Cov.: 33

Gnomad AFR AF: 0.0740

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00610

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.0144

GnomAD3 exomes AF: 0.00547 AC: 1376 AN: 251440 Hom.: 62 AF XY: 0.00398 AC XY: 541 AN XY: 135894

Gnomad AFR exome AF: 0.0771

Gnomad AMR exome AF: 0.00280

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000131

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000967

Gnomad OTH exome AF: 0.00179

GnomAD4 exome AF: 0.00212 AC: 3089 AN: 1457350 Hom.: 111 Cov.: 29 AF XY: 0.00181 AC XY: 1312 AN XY: 725366

Gnomad4 AFR exome AF: 0.0792

Gnomad4 AMR exome AF: 0.00300

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000151

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000379

Gnomad4 OTH exome AF: 0.00424

GnomAD4 genome AF: 0.0210 AC: 3196 AN: 152098 Hom.: 132 Cov.: 33 AF XY: 0.0202 AC XY: 1502 AN XY: 74342

Gnomad4 AFR AF: 0.0738

Gnomad4 AMR AF: 0.00609

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000147

Gnomad4 OTH AF: 0.0142

Alfa AF: 0.0107 Hom.: 20

Bravo AF: 0.0236

Asia WGS AF: 0.00346 AC: 13 AN: 3478

EpiCase AF: 0.000218

EpiControl AF: 0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	Aug 15, 2023	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	-	- -

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 18, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -

Lynch syndrome 8 Benign:2

Benign, criteria provided, single submitter	clinical testing	KCCC/NGS Laboratory, Kuwait Cancer Control Center	Jul 07, 2023	- -
Benign, criteria provided, single submitter	clinical testing	Counsyl	Sep 01, 2017	- -

Hereditary cancer-predisposing syndrome Benign:1

Likely benign, no assertion criteria provided

clinical testing

True Health Diagnostics

Jan 03, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	3.6
DANN	Benign	0.51
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000045
dbscSNV1_RF	Benign	0.0060
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

LitVar

Other links and lift over

dbSNP: rs72882786; hg19: chr2-47612298; COSMIC: COSV104560656; COSMIC: COSV104560656;