NM_002354.3:c.34C>G
Variant summary
Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate
The NM_002354.3(EPCAM):c.34C>G(p.Leu12Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000221 in 1,583,054 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L12R) has been classified as Uncertain significance.
Frequency
Consequence
NM_002354.3 missense
Scores
Clinical Significance
Conservation
Publications
- Lynch syndromeInheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
- Lynch syndrome 8Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, G2P, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
- congenital diarrhea 5 with tufting enteropathyInheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, Orphanet, G2P, Ambry Genetics
- hereditary breast carcinomaInheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
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ACMG classification
Our verdict: Likely_benign. The variant received -2 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152116Hom.: 0 Cov.: 32 show subpopulations
GnomAD2 exomes AF: 0.0000154 AC: 3AN: 195042 AF XY: 0.0000187 show subpopulations
GnomAD4 exome AF: 0.0000238 AC: 34AN: 1430938Hom.: 0 Cov.: 31 AF XY: 0.0000240 AC XY: 17AN XY: 709648 show subpopulations
Age Distribution
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152116Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74316 show subpopulations
Age Distribution
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:1
The p.L12V variant (also known as c.34C>G), located in coding exon 1 of the EPCAM gene, results from a C to G substitution at nucleotide position 34. The leucine at codon 12 is replaced by valine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at