rs62139669

Variant names:

• chr2-47386560-T-C
• rs62139669
• NM_002354.3:c.904-12T>C

Your query was ambiguous. Multiple possible variants found:

• chr2-47386560-T-C
• chr2-47386560-T-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.904-12T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0389 in 1,591,436 control chromosomes in the GnomAD database, including 1,405 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.034 (124 hom., cov: 33)
  • Exomes 𝑓: 0.039 (1281 hom.)
• Consequence: EPCAM NM_002354.3 intron
• Scores: Splicing: ADA: 0.00009840
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -1.60
• Publications: 3 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: Orphanet, ClinGen
• Lynch syndrome 8

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

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: PanelApp Australia, Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae), G2P
• 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=-0.78).
• BP6: Variant 2-47386560-T-C is Benign according to our data. Variant chr2-47386560-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 258645.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0584 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPCAM	NM_002354.3	MANE Select	c.904-12T>C		intron	N/A	NP_002345.2	P16422

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPCAM	ENST00000263735.9	TSL:1 MANE Select	c.904-12T>C		intron	N/A	ENSP00000263735.4	P16422
	EPCAM	ENST00000895681.1		c.922T>C	p.Phe308Leu	missense	Exon 9 of 9	ENSP00000565740.1
	EPCAM	ENST00000405271.5	TSL:5	c.988-12T>C		intron	N/A	ENSP00000385476.1	B5MCA4

Frequencies

GnomAD3 genomes AF: 0.0343 AC: 5221 AN: 152190 Hom.: 123 Cov.: 33

Gnomad AFR AF: 0.00825

Gnomad AMI AF: 0.0395

Gnomad AMR AF: 0.0617

Gnomad ASJ AF: 0.0378

Gnomad EAS AF: 0.000576

Gnomad SAS AF: 0.0566

Gnomad FIN AF: 0.0458

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0430

Gnomad OTH AF: 0.0363

GnomAD2 exomes AF: 0.0402 AC: 9992 AN: 248810 AF XY: 0.0411

Gnomad AFR exome AF: 0.00627

Gnomad AMR exome AF: 0.0561

Gnomad ASJ exome AF: 0.0419

Gnomad EAS exome AF: 0.000437

Gnomad FIN exome AF: 0.0467

Gnomad NFE exome AF: 0.0391

Gnomad OTH exome AF: 0.0392

GnomAD4 exome AF: 0.0394 AC: 56676 AN: 1439128 Hom.: 1281 Cov.: 27 AF XY: 0.0403 AC XY: 28826 AN XY: 716108

African (AFR) AF: 0.00530 AC: 176 AN: 33192

American (AMR) AF: 0.0548 AC: 2422 AN: 44182

Ashkenazi Jewish (ASJ) AF: 0.0399 AC: 1030 AN: 25840

East Asian (EAS) AF: 0.000228 AC: 9 AN: 39488

South Asian (SAS) AF: 0.0648 AC: 5361 AN: 82742

European-Finnish (FIN) AF: 0.0445 AC: 2355 AN: 52962

Middle Eastern (MID) AF: 0.0387 AC: 213 AN: 5508

European-Non Finnish (NFE) AF: 0.0391 AC: 42866 AN: 1095638

Other (OTH) AF: 0.0377 AC: 2244 AN: 59576

GnomAD4 genome AF: 0.0343 AC: 5222 AN: 152308 Hom.: 124 Cov.: 33 AF XY: 0.0361 AC XY: 2686 AN XY: 74484

African (AFR) AF: 0.00823 AC: 342 AN: 41568

American (AMR) AF: 0.0616 AC: 942 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0378 AC: 131 AN: 3468

East Asian (EAS) AF: 0.000578 AC: 3 AN: 5192

South Asian (SAS) AF: 0.0570 AC: 275 AN: 4822

European-Finnish (FIN) AF: 0.0458 AC: 486 AN: 10620

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0430 AC: 2927 AN: 68036

Other (OTH) AF: 0.0360 AC: 76 AN: 2114

Alfa AF: 0.0398 Hom.: 53

Bravo AF: 0.0318

Asia WGS AF: 0.0220 AC: 78 AN: 3472

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	not specified (5)
-	-	2	not provided (2)
-	-	1	Lynch syndrome 8 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	2.6
DANN	Benign	0.81
PhyloP100		-1.6
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000098
dbscSNV1_RF	Benign	0.0
SpliceAI score (max)		0.040		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: rs62139669; hg19: chr2-47613699; COSMIC: COSV107227826; COSMIC: COSV107227826;