chr2-47373890-G-C
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_002354.3(EPCAM):c.267G>C(p.Gln89His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00436 in 1,614,118 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. Q89Q) has been classified as Likely benign.
Frequency
Consequence
NM_002354.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EPCAM | NM_002354.3 | c.267G>C | p.Gln89His | missense_variant | 3/9 | ENST00000263735.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EPCAM | ENST00000263735.9 | c.267G>C | p.Gln89His | missense_variant | 3/9 | 1 | NM_002354.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00285 AC: 433AN: 152118Hom.: 3 Cov.: 32
GnomAD3 exomes AF: 0.00272 AC: 684AN: 251466Hom.: 3 AF XY: 0.00284 AC XY: 386AN XY: 135910
GnomAD4 exome AF: 0.00452 AC: 6604AN: 1461882Hom.: 22 Cov.: 33 AF XY: 0.00440 AC XY: 3198AN XY: 727246
GnomAD4 genome ? AF: 0.00284 AC: 433AN: 152236Hom.: 3 Cov.: 32 AF XY: 0.00257 AC XY: 191AN XY: 74418
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:7
Benign, criteria provided, single submitter | clinical testing | Invitae | Jul 19, 2022 | - - |
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, Amsterdam University Medical Center | - | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden | Nov 03, 2021 | - - |
Likely benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Aug 31, 2016 | Variant summary: The EPCAM c.267G>C (p.Gln89His) variant causes a missense change involving a non-conserved nucleotide with 2/3 in silico tools (SNPs&GO and Mutation Taster not captured here due to low reliability index and p-value, respectively) predicting a "damaging" outcome. The variant has been observed in the large, broad control population, ExAC, with an allele frequency of 313/121362 (1/387, 2 homozygotes), which significantly exceeds the estimated maximal expected allele frequency for a pathogenic EPCAM variant of 1/35211, suggesting this variant is likely a benign polymorphism. Multiple clinical diagnostic laboratories cite the variant as "likely benign/benign." Therefore, the variant of interest has been classified as Benign. - |
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Apr 04, 2017 | - - |
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Apr 01, 2024 | EPCAM: BP4, BS1, BS2 - |
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Apr 28, 2021 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Dec 24, 2013 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Hereditary cancer-predisposing syndrome Benign:2
Benign, criteria provided, single submitter | curation | Sema4, Sema4 | Jan 28, 2021 | - - |
Likely benign, no assertion criteria provided | clinical testing | True Health Diagnostics | Nov 15, 2017 | - - |
Lynch syndrome Benign:1
Likely benign, criteria provided, single submitter | research | CSER _CC_NCGL, University of Washington | Mar 11, 2015 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at