rs878854492

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 2P and 11B. PM2BP4_ModerateBP6_Very_StrongBP7

The NM_002354.3(EPCAM):c.558T>C(p.Tyr186Tyr) variant causes a splice region, 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. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

EPCAM
NM_002354.3 splice_region, synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.68

Publications

0 publications found

Variant links:

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

EPCAM links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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=-0.39).

BP6

Variant 2-47378955-T-C is Benign according to our data. Variant chr2-47378955-T-C is described in CliVar as Likely_benign. Clinvar id is 239133.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-47378955-T-C is described in CliVar as Likely_benign. Clinvar id is 239133.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-47378955-T-C is described in CliVar as Likely_benign. Clinvar id is 239133.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-47378955-T-C is described in CliVar as Likely_benign. Clinvar id is 239133.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-47378955-T-C is described in CliVar as Likely_benign. Clinvar id is 239133.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-47378955-T-C is described in CliVar as Likely_benign. Clinvar id is 239133.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-47378955-T-C is described in CliVar as Likely_benign. Clinvar id is 239133.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-47378955-T-C is described in CliVar as Likely_benign. Clinvar id is 239133.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-47378955-T-C is described in CliVar as Likely_benign. Clinvar id is 239133.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-47378955-T-C is described in CliVar as Likely_benign. Clinvar id is 239133.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=2.68 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPCAM	NM_002354.3 link	c.558T>C	p.Tyr186Tyr	splice_region_variant, synonymous_variant	Exon 6 of 9	ENST00000263735.9	NP_002345.2	P16422

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
EPCAM	ENST00000263735.9 link	c.558T>C	p.Tyr186Tyr	splice_region_variant, synonymous_variant	Exon 6 of 9	1	NM_002354.3	ENSP00000263735.4	P16422
EPCAM	ENST00000405271.5 link	c.642T>C	p.Tyr214Tyr	splice_region_variant, synonymous_variant	Exon 7 of 10	5		ENSP00000385476.1	B5MCA4
EPCAM	ENST00000456133.5 link	n.642T>C		splice_region_variant, non_coding_transcript_exon_variant	Exon 7 of 11	5		ENSP00000410675.1	B5MCA4
EPCAM	ENST00000490733.1 link	n.407T>C		splice_region_variant, non_coding_transcript_exon_variant	Exon 4 of 6	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1284330

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

649040

African (AFR)

AF:

0.00

AC:

AN:

29922

American (AMR)

AF:

0.00

AC:

AN:

44492

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25008

East Asian (EAS)

AF:

0.00

AC:

AN:

38726

South Asian (SAS)

AF:

0.00

AC:

AN:

82466

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53238

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5102

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

950928

Other (OTH)

AF:

0.00

AC:

AN:

54448

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Sep 30, 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

Feb 02, 2024

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

-0.39

CADD

Benign

(source)

DANN

Benign

0.89

PhyloP100

2.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=88/12

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over