chr16-68828300-A-T
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM1PM2PP3_Strong
The NM_004360.5(CDH1):c.2291A>T(p.Asp764Val) 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D764E) has been classified as Uncertain significance.
Frequency
Consequence
NM_004360.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CDH1 | NM_004360.5 | c.2291A>T | p.Asp764Val | missense_variant | 14/16 | ENST00000261769.10 | |
CDH1 | NM_001317184.2 | c.2108A>T | p.Asp703Val | missense_variant | 13/15 | ||
CDH1 | NM_001317185.2 | c.743A>T | p.Asp248Val | missense_variant | 14/16 | ||
CDH1 | NM_001317186.2 | c.326A>T | p.Asp109Val | missense_variant | 13/15 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDH1 | ENST00000261769.10 | c.2291A>T | p.Asp764Val | missense_variant | 14/16 | 1 | NM_004360.5 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome Cov.: 32
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Hereditary diffuse gastric adenocarcinoma Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 15, 2022 | This sequence change replaces aspartic acid, which is acidic and polar, with valine, which is neutral and non-polar, at codon 764 of the CDH1 protein (p.Asp764Val). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with gastric cancer (Invitae). ClinVar contains an entry for this variant (Variation ID: 1465174). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). This variant disrupts the p.Asp764 amino acid residue in CDH1. Other variant(s) that disrupt this residue have been observed in individuals with CDH1-related conditions (Invitae), which suggests that this may be a clinically significant amino acid residue. In summary, the available evidence is currently insufficient to determine the role of this variant 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
Publications
No publications associated with this variant yet.