rs864622724
Variant summary
Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.
The NM_002354.3(EPCAM):c.450C>G(p.His150Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000023 in 1,611,798 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. H150R) 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
Genome browser will be placed here
ACMG classification
Our verdict: Uncertain_significance. The variant received 0 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000460 AC: 7AN: 152138Hom.: 0 Cov.: 33 show subpopulations
GnomAD2 exomes AF: 0.00000796 AC: 2AN: 251282 AF XY: 0.00 show subpopulations
GnomAD4 exome AF: 0.0000206 AC: 30AN: 1459660Hom.: 0 Cov.: 29 AF XY: 0.0000220 AC XY: 16AN XY: 726260 show subpopulations
GnomAD4 genome AF: 0.0000460 AC: 7AN: 152138Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74316 show subpopulations
ClinVar
Submissions by phenotype
not provided Uncertain:1
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 sequence change replaces histidine with glutamine at codon 150 of the EPCAM protein (p.His150Gln). The histidine residue is highly conserved and there is a small physicochemical difference between histidine and glutamine. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, this is a rare missense change with uncertain impact on protein function. There is no indication that this variant causes disease, but the evidence is insufficient at this time to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at