rs786204058
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 6P and 1B. PM1PM2PM5BP4
The ENST00000261769.10(CDH1):c.1679C>A(p.Thr560Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,542 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign 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. T560R) has been classified as Pathogenic.
Frequency
Consequence
ENST00000261769.10 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CDH1 | NM_004360.5 | c.1679C>A | p.Thr560Lys | missense_variant | 11/16 | ENST00000261769.10 | NP_004351.1 | |
CDH1 | NM_001317184.2 | c.1496C>A | p.Thr499Lys | missense_variant | 10/15 | NP_001304113.1 | ||
CDH1 | NM_001317185.2 | c.131C>A | p.Thr44Lys | missense_variant | 11/16 | NP_001304114.1 | ||
CDH1 | NM_001317186.2 | c.-254-2608C>A | intron_variant | NP_001304115.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CDH1 | ENST00000261769.10 | c.1679C>A | p.Thr560Lys | missense_variant | 11/16 | 1 | NM_004360.5 | ENSP00000261769 | P1 | |
ENST00000563916.1 | n.264-3734G>T | intron_variant, non_coding_transcript_variant | 4 |
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461542Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 727064
GnomAD4 genome Cov.: 31
ClinVar
Submissions by phenotype
Hereditary diffuse gastric adenocarcinoma Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Sep 01, 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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 1043223). This variant has not been reported in the literature in individuals affected with CDH1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces threonine, which is neutral and polar, with lysine, which is basic and polar, at codon 560 of the CDH1 protein (p.Thr560Lys). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at