16-68738303-T-G
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBS2_Supporting
The NM_004360.5(CDH1):āc.55T>Gā(p.Ser19Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000358 in 1,397,286 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ).
Frequency
Consequence
NM_004360.5 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CDH1 | NM_004360.5 | c.55T>G | p.Ser19Ala | missense_variant | 2/16 | ENST00000261769.10 | NP_004351.1 | |
CDH1 | NM_001317184.2 | c.55T>G | p.Ser19Ala | missense_variant | 2/15 | NP_001304113.1 | ||
CDH1 | NM_001317185.2 | c.-1561T>G | 5_prime_UTR_variant | 2/16 | NP_001304114.1 | |||
CDH1 | NM_001317186.2 | c.-1765T>G | 5_prime_UTR_variant | 2/15 | NP_001304115.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CDH1 | ENST00000261769.10 | c.55T>G | p.Ser19Ala | missense_variant | 2/16 | 1 | NM_004360.5 | ENSP00000261769.4 | ||
CDH1 | ENST00000422392.6 | c.55T>G | p.Ser19Ala | missense_variant | 2/15 | 1 | ENSP00000414946.2 | |||
CDH1 | ENST00000566612.5 | n.55T>G | non_coding_transcript_exon_variant | 2/15 | 1 | ENSP00000454782.1 | ||||
CDH1 | ENST00000566510.5 | n.55T>G | non_coding_transcript_exon_variant | 2/15 | 5 | ENSP00000458139.1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000636 AC: 1AN: 157190Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 82962
GnomAD4 exome AF: 0.00000358 AC: 5AN: 1397286Hom.: 0 Cov.: 30 AF XY: 0.00000290 AC XY: 2AN XY: 689382
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Hereditary diffuse gastric adenocarcinoma Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Aug 23, 2023 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The alanine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 406626). This variant has not been reported in the literature in individuals affected with CDH1-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.004%). This sequence change replaces serine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 19 of the CDH1 protein (p.Ser19Ala). - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 01, 2018 | The p.S19A variant (also known as c.55T>G), located in coding exon 2 of the CDH1 gene, results from a T to G substitution at nucleotide position 55. The serine at codon 19 is replaced by alanine, an amino acid with similar properties. This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at