chr2-47385017-A-G

Position:

• chr2-47385017-A-G

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.859-149A>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

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 Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EPCAM	NM_002354.3	c.859-149A>G		intron_variant		ENST00000263735.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EPCAM	ENST00000263735.9	c.859-149A>G		intron_variant		1	NM_002354.3	P1
EPCAM	ENST00000405271.5	c.943-149A>G		intron_variant		5
EPCAM	ENST00000456133.5	c.943-149A>G		intron_variant, NMD_transcript_variant		5
EPCAM	ENST00000490733.1	n.708-149A>G		intron_variant, non_coding_transcript_variant		3

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

Gnomad4 AFR exome AF: 0.158

Gnomad4 AMR exome AF: 0.131

Gnomad4 ASJ exome AF: 0.0526

Gnomad4 EAS exome AF: 0.183

Gnomad4 SAS exome AF: 0.0926

Gnomad4 FIN exome AF: 0.0993

Gnomad4 NFE exome AF: 0.0720

Gnomad4 OTH exome AF: 0.0857

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

Gnomad4 AFR AF: 0.152

Gnomad4 AMR AF: 0.101

Gnomad4 ASJ AF: 0.0637

Gnomad4 EAS AF: 0.173

Gnomad4 SAS AF: 0.108

Gnomad4 FIN AF: 0.100

Gnomad4 NFE AF: 0.0717

Gnomad4 OTH AF: 0.0918

Alfa AF: 0.0726 Hom.: 741

Bravo AF: 0.105

Asia WGS AF: 0.157 AC: 547 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 06, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.89
DANN	Benign	0.65

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

LitVar

Other links and lift over

dbSNP: rs4952886; hg19: chr2-47612156;