chr2-47378990-ATTC-A

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PM4_Supporting

The NM_002354.3(EPCAM):c.598_600delTCT(p.Ser200del) variant causes a conservative inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000117 in 1,449,708 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

EPCAM
NM_002354.3 conservative_inframe_deletion

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:2

Conservation

PhyloP100: 1.35

Publications

1 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: Uncertain_significance. The variant received 1 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_002354.3. Strenght limited to Supporting due to length of the change: 1aa.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPCAM	NM_002354.3 link	c.598_600delTCT	p.Ser200del	conservative_inframe_deletion	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.598_600delTCT	p.Ser200del	conservative_inframe_deletion	Exon 6 of 9	1	NM_002354.3	ENSP00000263735.4	P16422
EPCAM	ENST00000405271.5 link	c.682_684delTCT	p.Ser228del	conservative_inframe_deletion	Exon 7 of 10	5		ENSP00000385476.1	B5MCA4
EPCAM	ENST00000456133.5 link	n.682_684delTCT		non_coding_transcript_exon_variant	Exon 7 of 11	5		ENSP00000410675.1	B5MCA4
EPCAM	ENST00000490733.1 link	n.447_449delTCT		non_coding_transcript_exon_variant	Exon 4 of 6	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000239

AC:

AN:

251194

AF XY:

0.0000147

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000528

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000117

AC:

AN:

1449708

Hom.:

AF XY:

0.00000831

AC XY:

AN XY:

722084

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33236

American (AMR)

AF:

0.0000224

AC:

AN:

44692

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26054

East Asian (EAS)

AF:

0.00

AC:

AN:

39564

South Asian (SAS)

AF:

0.00

AC:

AN:

86032

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53378

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5662

European-Non Finnish (NFE)

AF:

0.0000145

AC:

AN:

1101106

Other (OTH)

AF:

0.00

AC:

AN:

59984

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.449

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000340

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Lynch syndrome

Uncertain:1

Jan 01, 2016

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This sequence change deletes 3 nucleotides from exon 6 of the EPCAM mRNA (c.598_600delTCT). This leads to the deletion of 1 amino acid residue in the EPCAM protein (p.Ser200del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs775898569, ExAC <0.01%) but has not been reported in the literature in individuals with an EPCAM-related disease. ClinVar contains an entry for this variant (Variation ID: 216872). In summary, this is a rare in-frame deletion with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance. -

Hereditary nonpolyposis colorectal neoplasms

Uncertain:1

Sep 17, 2021

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant, c.598_600del, results in the deletion of 1 amino acid(s) of the EPCAM protein (p.Ser200del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs775898569, ExAC 0.006%). This variant has not been reported in the literature in individuals affected with EPCAM-related conditions. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.3

Mutation Taster

=51/49

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

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over