16-68833427-T-A
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PVS1_ModeratePM2
The NM_004360.5(CDH1):c.2577T>A(p.Tyr859Ter) variant causes a stop gained change involving the alteration of a non-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 (★). Synonymous variant affecting the same amino acid position (i.e. Y859Y) has been classified as Likely benign.
Frequency
Consequence
NM_004360.5 stop_gained
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CDH1 | NM_004360.5 | c.2577T>A | p.Tyr859Ter | stop_gained | 16/16 | ENST00000261769.10 | |
CDH1 | NM_001317184.2 | c.2394T>A | p.Tyr798Ter | stop_gained | 15/15 | ||
CDH1 | NM_001317185.2 | c.1029T>A | p.Tyr343Ter | stop_gained | 16/16 | ||
CDH1 | NM_001317186.2 | c.612T>A | p.Tyr204Ter | stop_gained | 15/15 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDH1 | ENST00000261769.10 | c.2577T>A | p.Tyr859Ter | stop_gained | 16/16 | 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 | Nov 11, 2019 | This sequence change results in a premature translational stop signal in the CDH1 gene (p.Tyr859*). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 24 amino acids of the CDH1 protein. This variant is not present in population databases (ExAC no frequency). 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. This variant has not been reported in the literature in individuals with CDH1-related conditions. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at