chr2-47385017-A-G

Variant names:

• chr2-47385017-A-G
• rs4952886
• NM_002354.3:c.859-149A>G

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.859-149A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0919 in 674,418 control chromosomes in the GnomAD database, including 3,317 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.10 (919 hom., cov: 33)
  • Exomes 𝑓: 0.089 (2398 hom.)
• Consequence: EPCAM NM_002354.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.242
• Publications: 7 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=-0.86).
• BP6: Variant 2-47385017-A-G is Benign according to our data. Variant chr2-47385017-A-G is described in ClinVar as Benign. ClinVar VariationId is 1244355.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.163 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002354.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPCAM	NM_002354.3	MANE Select	c.859-149A>G		intron	N/A	NP_002345.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPCAM	ENST00000263735.9	TSL:1 MANE Select	c.859-149A>G		intron	N/A	ENSP00000263735.4
	EPCAM	ENST00000405271.5	TSL:5	c.943-149A>G		intron	N/A	ENSP00000385476.1
	EPCAM	ENST00000895681.1		c.859-149A>G		intron	N/A	ENSP00000565740.1

Frequencies

GnomAD3 genomes AF: 0.103 AC: 15672 AN: 152088 Hom.: 917 Cov.: 33

Gnomad AFR AF: 0.153

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.0637

Gnomad EAS AF: 0.172

Gnomad SAS AF: 0.109

Gnomad FIN AF: 0.100

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0717

Gnomad OTH AF: 0.0908

GnomAD4 exome AF: 0.0886 AC: 46271 AN: 522212 Hom.: 2398 AF XY: 0.0874 AC XY: 24704 AN XY: 282742

African (AFR) AF: 0.158 AC: 2187 AN: 13860

American (AMR) AF: 0.131 AC: 3964 AN: 30206

Ashkenazi Jewish (ASJ) AF: 0.0526 AC: 863 AN: 16398

East Asian (EAS) AF: 0.183 AC: 5690 AN: 31050

South Asian (SAS) AF: 0.0926 AC: 5366 AN: 57976

European-Finnish (FIN) AF: 0.0993 AC: 3693 AN: 37174

Middle Eastern (MID) AF: 0.0647 AC: 173 AN: 2674

European-Non Finnish (NFE) AF: 0.0720 AC: 22000 AN: 305616

Other (OTH) AF: 0.0857 AC: 2335 AN: 27258

GnomAD4 genome AF: 0.103 AC: 15683 AN: 152206 Hom.: 919 Cov.: 33 AF XY: 0.105 AC XY: 7850 AN XY: 74428

African (AFR) AF: 0.152 AC: 6325 AN: 41524

American (AMR) AF: 0.101 AC: 1550 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0637 AC: 221 AN: 3470

East Asian (EAS) AF: 0.173 AC: 895 AN: 5180

South Asian (SAS) AF: 0.108 AC: 522 AN: 4822

European-Finnish (FIN) AF: 0.100 AC: 1062 AN: 10604

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0717 AC: 4879 AN: 68010

Other (OTH) AF: 0.0918 AC: 194 AN: 2114

Alfa AF: 0.0802 Hom.: 1962

Bravo AF: 0.105

Asia WGS AF: 0.157 AC: 547 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.89
DANN	Benign	0.65
PhyloP100		-0.24
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: rs4952886; hg19: chr2-47612156;