rs1555517817
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The NM_004360.5(CDH1):c.2296-12T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,772 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )
Consequence
CDH1
NM_004360.5 intron
NM_004360.5 intron
Scores
2
Splicing: ADA: 0.00006851
2
Clinical Significance
Conservation
PhyloP100: 0.597
Genes affected
CDH1 (HGNC:1748): (cadherin 1) This gene encodes a classical cadherin of the cadherin superfamily. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed to generate the mature glycoprotein. This calcium-dependent cell-cell adhesion protein is comprised of five extracellular cadherin repeats, a transmembrane region and a highly conserved cytoplasmic tail. Mutations in this gene are correlated with gastric, breast, colorectal, thyroid and ovarian cancer. Loss of function of this gene is thought to contribute to cancer progression by increasing proliferation, invasion, and/or metastasis. The ectodomain of this protein mediates bacterial adhesion to mammalian cells and the cytoplasmic domain is required for internalization. This gene is present in a gene cluster with other members of the cadherin family on chromosome 16. [provided by RefSeq, Nov 2015]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.76).
BP6
Variant 16-68829642-T-C is Benign according to our data. Variant chr16-68829642-T-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 489856.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=1}.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| CDH1 | NM_004360.5 | c.2296-12T>C | intron_variant | Intron 14 of 15 | ENST00000261769.10 | NP_004351.1 | ||
| CDH1 | NM_001317184.2 | c.2113-12T>C | intron_variant | Intron 13 of 14 | NP_001304113.1 | |||
| CDH1 | NM_001317185.2 | c.748-12T>C | intron_variant | Intron 14 of 15 | NP_001304114.1 | |||
| CDH1 | NM_001317186.2 | c.331-12T>C | intron_variant | Intron 13 of 14 | NP_001304115.1 |
Ensembl
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461772Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 727174
GnomAD4 exome
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3
AN:
1461772
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32
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1
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727174
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GnomAD4 genome
GnomAD4 genome
Cov.:
32
Bravo
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:2
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Hereditary diffuse gastric adenocarcinoma Benign:2
Sep 23, 2024
Myriad Genetics, Inc.
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
This variant is considered likely benign. This variant is intronic and is not expected to impact mRNA splicing. -
Dec 23, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
Hereditary cancer-predisposing syndrome Uncertain:1
Apr 13, 2019
Color Diagnostics, LLC DBA Color Health
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at