2-47385085-C-T

Variant names:

• chr2-47385085-C-T
• rs7584256
• NM_002354.3:c.859-81C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002354.3(EPCAM):​c.859-81C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.283 in 1,011,288 control chromosomes in the GnomAD database, including 43,193 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.30 (7452 hom., cov: 33)
  • Exomes 𝑓: 0.28 (35741 hom.)
• Consequence: EPCAM NM_002354.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.653
• Publications: 11 publications found

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 Gene-Disease associations (from GenCC):

• Lynch syndrome

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
• Lynch syndrome 8

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, G2P, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
• congenital diarrhea 5 with tufting enteropathy

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, Orphanet, G2P, Ambry Genetics
• hereditary breast carcinoma

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 2-47385085-C-T is Benign according to our data. Variant chr2-47385085-C-T is described in ClinVar as Benign. ClinVar VariationId is 1225243.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.534 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPCAM	NM_002354.3	c.859-81C>T		intron_variant	Intron 7 of 8	ENST00000263735.9	NP_002345.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPCAM	ENST00000263735.9	c.859-81C>T		intron_variant	Intron 7 of 8	1	NM_002354.3	ENSP00000263735.4
EPCAM	ENST00000405271.5	c.943-81C>T		intron_variant	Intron 8 of 9	5		ENSP00000385476.1
EPCAM	ENST00000456133.5	n.943-81C>T		intron_variant	Intron 8 of 10	5		ENSP00000410675.1
EPCAM	ENST00000490733.1	n.708-81C>T		intron_variant	Intron 5 of 5	3

Frequencies

GnomAD3 genomes AF: 0.304 AC: 46205 AN: 151880 Hom.: 7447 Cov.: 33

Gnomad AFR AF: 0.354

Gnomad AMI AF: 0.237

Gnomad AMR AF: 0.267

Gnomad ASJ AF: 0.212

Gnomad EAS AF: 0.552

Gnomad SAS AF: 0.292

Gnomad FIN AF: 0.369

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.261

Gnomad OTH AF: 0.289

GnomAD4 exome AF: 0.279 AC: 239970 AN: 859290 Hom.: 35741 AF XY: 0.278 AC XY: 125661 AN XY: 452144

African (AFR) AF: 0.357 AC: 7656 AN: 21472

American (AMR) AF: 0.247 AC: 10604 AN: 42992

Ashkenazi Jewish (ASJ) AF: 0.221 AC: 4884 AN: 22120

East Asian (EAS) AF: 0.519 AC: 19016 AN: 36626

South Asian (SAS) AF: 0.278 AC: 20328 AN: 73172

European-Finnish (FIN) AF: 0.372 AC: 19447 AN: 52224

Middle Eastern (MID) AF: 0.223 AC: 1009 AN: 4532

European-Non Finnish (NFE) AF: 0.257 AC: 145259 AN: 565858

Other (OTH) AF: 0.292 AC: 11767 AN: 40294

GnomAD4 genome AF: 0.304 AC: 46254 AN: 151998 Hom.: 7452 Cov.: 33 AF XY: 0.308 AC XY: 22867 AN XY: 74274

African (AFR) AF: 0.354 AC: 14670 AN: 41438

American (AMR) AF: 0.267 AC: 4075 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.212 AC: 734 AN: 3468

East Asian (EAS) AF: 0.551 AC: 2855 AN: 5184

South Asian (SAS) AF: 0.293 AC: 1412 AN: 4826

European-Finnish (FIN) AF: 0.369 AC: 3890 AN: 10528

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.261 AC: 17735 AN: 67970

Other (OTH) AF: 0.288 AC: 608 AN: 2108

Alfa AF: 0.276 Hom.: 3181

Bravo AF: 0.300

Asia WGS AF: 0.403 AC: 1398 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.1
DANN	Benign	0.44
PhyloP100		-0.65
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7584256; hg19: chr2-47612224; COSMIC: COSV55395062; COSMIC: COSV55395062;