rs1555518224
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_004360.5(CDH1):c.2480A>G(p.Tyr827Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_004360.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CDH1 | NM_004360.5 | c.2480A>G | p.Tyr827Cys | missense_variant | Exon 16 of 16 | ENST00000261769.10 | NP_004351.1 | |
CDH1 | NM_001317184.2 | c.2297A>G | p.Tyr766Cys | missense_variant | Exon 15 of 15 | NP_001304113.1 | ||
CDH1 | NM_001317185.2 | c.932A>G | p.Tyr311Cys | missense_variant | Exon 16 of 16 | NP_001304114.1 | ||
CDH1 | NM_001317186.2 | c.515A>G | p.Tyr172Cys | missense_variant | Exon 15 of 15 | NP_001304115.1 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 32
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Hereditary diffuse gastric adenocarcinoma Uncertain:1
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: "Probably Damaging"; Align-GVGD: "Class C0"). This sequence change replaces tyrosine with cysteine at codon 827 of the CDH1 protein (p.Tyr827Cys). The tyrosine residue is highly conserved and there is a large physicochemical difference between tyrosine and cysteine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with a CDH1-related disease. In summary, this variant has uncertain impact on CDH1 function. The available evidence is currently insufficient to determine its role in disease. 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