Genetic Variant EPCAM:p.Ala22_Ala23insAlaThrAlaThrPheAlaAla (chr2-47369542-C-CTTGCCGCGGCGACGGCGACTT) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM4

The NM_002354.3(EPCAM):c.45_65dupGGCGACGGCGACTTTTGCCGC(p.Ala22_Ala23insAlaThrAlaThrPheAlaAla) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000698 in 1,432,394 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A22A) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

EPCAM
NM_002354.3 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.68

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: Uncertain_significance. The variant received 2 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_002354.3.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPCAM	NM_002354.3	MANE Select	c.45_65dupGGCGACGGCGACTTTTGCCGC	p.Ala22_Ala23insAlaThrAlaThrPheAlaAla	disruptive_inframe_insertion	Exon 1 of 9	NP_002345.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
EPCAM	ENST00000263735.9	TSL:1 MANE Select	c.45_65dupGGCGACGGCGACTTTTGCCGC	p.Ala22_Ala23insAlaThrAlaThrPheAlaAla	disruptive_inframe_insertion	Exon 1 of 9	ENSP00000263735.4
EPCAM	ENST00000895681.1		c.45_65dupGGCGACGGCGACTTTTGCCGC	p.Ala22_Ala23insAlaThrAlaThrPheAlaAla	disruptive_inframe_insertion	Exon 1 of 9	ENSP00000565740.1
EPCAM	ENST00000895685.1		c.45_65dupGGCGACGGCGACTTTTGCCGC	p.Ala22_Ala23insAlaThrAlaThrPheAlaAla	disruptive_inframe_insertion	Exon 1 of 9	ENSP00000565744.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.98e-7

AC:

AN:

1432394

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

710430

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32460

American (AMR)

AF:

0.00

AC:

AN:

40186

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25398

East Asian (EAS)

AF:

0.00

AC:

AN:

38418

South Asian (SAS)

AF:

0.00

AC:

AN:

81824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48342

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4578

European-Non Finnish (NFE)

AF:

9.08e-7

AC:

AN:

1101870

Other (OTH)

AF:

0.00

AC:

AN:

59318

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

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.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.7

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

2-47369542-CTTGCCGCGGCGACGGCGACTT-CTTGCCGCGGCGACGGCGACTTTTGCCGCGGCGACGGCGACTT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over