rs864622092
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM4
The NM_002354.3(EPCAM):βc.45_65delβ(p.Thr17_Ala23del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000114 in 1,584,554 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (β β ).
Frequency
Genomes: π 0.000020 ( 0 hom., cov: 32)
Exomes π: 0.000010 ( 0 hom. )
Consequence
EPCAM
NM_002354.3 inframe_deletion
NM_002354.3 inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 3.44
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM4
?
Nonframeshift variant in NON repetitive region in NM_002354.3.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EPCAM | NM_002354.3 | c.45_65del | p.Thr17_Ala23del | inframe_deletion | 1/9 | ENST00000263735.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EPCAM | ENST00000263735.9 | c.45_65del | p.Thr17_Ala23del | inframe_deletion | 1/9 | 1 | NM_002354.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152160Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.0000105 AC: 15AN: 1432394Hom.: 0 AF XY: 0.0000141 AC XY: 10AN XY: 710430
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GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152160Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74328
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Lynch syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 06, 2015 | This sequence change deletes 21 nucleotides from exon 1 of the EPCAM mRNA (c.38_58delTTGCCGCGGCGACGGCGACTT). This leads to the deletion of 7 amino acid residues in the EPCAM protein (p.Ala14_Phe20del) but otherwise preserves the integrity of the reading frame. This variant has not been published in the literature and is not present in population databases. This deletion is in a region that encodes the signal peptide for EPCAM protein (PMID: 23618806) and signal peptides are known to be important for membrane localization during protein synthesis. However, there is no functional evidence that deletion of this region impacts EPCAM protein synthesis and/or localization. In summary, this is a novel variant with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Mar 01, 2023 | - - |
Hereditary nonpolyposis colorectal neoplasms Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 17, 2021 | - - |
Computational scores
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at