chr2-47369548-GCGGCGA-G
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Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PM4
The ENST00000263735.9(EPCAM):βc.51_56delβ(p.Ala18_Thr19del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000946 in 1,586,232 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (β ). Synonymous variant affecting the same amino acid position (i.e. A15A) has been classified as Likely benign.
Frequency
Genomes: π 0.0000066 ( 0 hom., cov: 32)
Exomes π: 0.0000098 ( 0 hom. )
Consequence
EPCAM
ENST00000263735.9 inframe_deletion
ENST00000263735.9 inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 1.29
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 4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PM4
Nonframeshift variant in NON repetitive region in ENST00000263735.9.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| EPCAM | NM_002354.3 | c.51_56del | p.Ala18_Thr19del | inframe_deletion | 1/9 | ENST00000263735.9 | NP_002345.2 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| EPCAM | ENST00000263735.9 | c.51_56del | p.Ala18_Thr19del | inframe_deletion | 1/9 | 1 | NM_002354.3 | ENSP00000263735 | P1 |
Frequencies
GnomAD3 genomes 0.00000657 AC: 1AN: 152154Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000100 AC: 2AN: 199900Hom.: 0 AF XY: 0.0000183 AC XY: 2AN XY: 109370
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GnomAD4 exome AF: 0.00000976 AC: 14AN: 1434078Hom.: 0 AF XY: 0.00000843 AC XY: 6AN XY: 711338
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GnomAD4 genome 0.00000657 AC: 1AN: 152154Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74314
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Lynch syndrome Uncertain:1
| Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 07, 2016 | This sequence change deletes 6 nucleotides from exon 1 of the EPCAM mRNA (c.51_56delGGCGAC). This leads to the deletion of 2 amino acid residues in the EPCAM protein (p.Ala18_Thr19del) but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a EPCAM-related disease. 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. - |
Hereditary nonpolyposis colorectal neoplasms Uncertain:1
| Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 07, 2016 | This sequence change deletes 6 nucleotides from exon 1 of the EPCAM mRNA (c.51_56delGGCGAC). This leads to the deletion of 2 amino acid residues in the EPCAM protein (p.Ala18_Thr19del) but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a EPCAM-related disease. 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. - |
Computational scores
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at