rs878854498

Variant names:

• chr2-47373485-G-A
• rs878854498
• NM_002354.3:c.99G>A

Your query was ambiguous. Multiple possible variants found:

• chr2-47373485-G-A
• chr2-47373485-G-C

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 2P and 11B. PM2 BP4_Moderate BP6_Very_Strong BP7

The NM_002354.3(EPCAM):​c.99G>A​(p.Lys33Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: EPCAM NM_002354.3 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.919
• Publications: 0 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 -9 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP6: Variant 2-47373485-G-A is Benign according to our data. Variant chr2-47373485-G-A is described in CliVar as Likely_benign. Clinvar id is 239146.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-47373485-G-A is described in CliVar as Likely_benign. Clinvar id is 239146.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-47373485-G-A is described in CliVar as Likely_benign. Clinvar id is 239146.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-47373485-G-A is described in CliVar as Likely_benign. Clinvar id is 239146.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-47373485-G-A is described in CliVar as Likely_benign. Clinvar id is 239146.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-47373485-G-A is described in CliVar as Likely_benign. Clinvar id is 239146.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-47373485-G-A is described in CliVar as Likely_benign. Clinvar id is 239146.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-47373485-G-A is described in CliVar as Likely_benign. Clinvar id is 239146.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-47373485-G-A is described in CliVar as Likely_benign. Clinvar id is 239146.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-47373485-G-A is described in CliVar as Likely_benign. Clinvar id is 239146.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-47373485-G-A is described in CliVar as Likely_benign. Clinvar id is 239146.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.919 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPCAM	NM_002354.3	c.99G>A	p.Lys33Lys	synonymous_variant	Exon 2 of 9	ENST00000263735.9	NP_002345.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPCAM	ENST00000263735.9	c.99G>A	p.Lys33Lys	synonymous_variant	Exon 2 of 9	1	NM_002354.3	ENSP00000263735.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Jan 04, 2016

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Hereditary cancer-predisposing syndrome Benign:1

May 14, 2019

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	5.2
DANN	Benign	0.76
PhyloP100		0.92
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

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: rs878854498; hg19: chr2-47600624;