16-68813403-G-C
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_004360.5(CDH1):c.1228G>C(p.Glu410Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. E410E) has been classified as Likely benign.
Frequency
Consequence
NM_004360.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CDH1 | NM_004360.5 | c.1228G>C | p.Glu410Gln | missense_variant | 9/16 | ENST00000261769.10 | |
CDH1 | NM_001317185.2 | c.-388G>C | 5_prime_UTR_variant | 9/16 | |||
CDH1 | NM_001317186.2 | c.-592G>C | 5_prime_UTR_variant | 9/15 | |||
CDH1 | NM_001317184.2 | c.1137+1140G>C | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDH1 | ENST00000261769.10 | c.1228G>C | p.Glu410Gln | missense_variant | 9/16 | 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 | Feb 06, 2016 | In summary, this is a novel missense change that is not predicted to affect protein function or cause disease. However, the evidence is insufficient at this time to prove that conclusively. It has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies. In addition, the glutamine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a CDH1-related disease. This sequence change replaces glutamic acid with glutamine at codon 410 of the CDH1 protein (p.Glu410Gln). The glutamic acid residue is weakly conserved and there is a small physicochemical difference between glutamic acid and glutamine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at