chr16-68810233-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1PM2BP4_Moderate
The NM_004360.5(CDH1):c.724G>C(p.Val242Leu) 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V242I) has been classified as Likely benign.
Frequency
Consequence
NM_004360.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CDH1 | NM_004360.5 | c.724G>C | p.Val242Leu | missense_variant | 6/16 | ENST00000261769.10 | |
CDH1 | NM_001317184.2 | c.724G>C | p.Val242Leu | missense_variant | 6/15 | ||
CDH1 | NM_001317185.2 | c.-892G>C | 5_prime_UTR_variant | 6/16 | |||
CDH1 | NM_001317186.2 | c.-1096G>C | 5_prime_UTR_variant | 6/15 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDH1 | ENST00000261769.10 | c.724G>C | p.Val242Leu | missense_variant | 6/16 | 1 | NM_004360.5 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 32
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jul 20, 2016 | This variant is denoted CDH1 c.724G>C at the cDNA level, p.Val242Leu (V242L) at the protein level, and results in the change of a Valine to a Leucine (GTT>CTT). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. CDH1 Val242Leu was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. Since Valine and Leucine share similar properties, this is considered a conservative amino acid substitution. CDH1 Val242Leu occurs at a position where amino acids with properties similar to Valine are tolerated across species and is located in the Cadherin 1 extracellular topological domain (Brooks-Wilson 2004, Figueiredo 2013, UniProt). In silico analyses predict that this variant is unlikely to alter protein structure or function. Based on currently available evidence, it is unclear whether CDH1 Val242Leu is a pathogenic or benign variant. We consider it to be a variant of uncertain significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at