ClinVar Genomic variation as it relates to human health
NM_004360.5(CDH1):c.532-18C>T
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_004360.5(CDH1):c.532-18C>T
Variation ID: 127931 Accession: VCV000127931.62
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 16q22.1 16: 68808675 (GRCh38) [ NCBI UCSC ] 16: 68842578 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Jan 31, 2016 Apr 15, 2024 Mar 1, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_004360.5:c.532-18C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
intron variant NM_001317184.2:c.532-18C>T intron variant NM_001317185.2:c.-1084-18C>T intron variant NM_001317186.2:c.-1288-18C>T intron variant NC_000016.10:g.68808675C>T NC_000016.9:g.68842578C>T NG_008021.1:g.76384C>T LRG_301:g.76384C>T LRG_301t1:c.532-18C>T - Protein change
- Other names
- IVS4-18C>T
- Canonical SPDI
- NC_000016.10:68808674:C:T
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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0.00020 (T)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
1000 Genomes Project 30x 0.00016
1000 Genomes Project 0.00020
Exome Aggregation Consortium (ExAC) 0.00346
The Genome Aggregation Database (gnomAD), exomes 0.00347
The Genome Aggregation Database (gnomAD) 0.00398
Trans-Omics for Precision Medicine (TOPMed) 0.00424
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00446
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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CDH1 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
4338 | 4425 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Benign/Likely benign (4) |
criteria provided, multiple submitters, no conflicts
|
May 2, 2021 | RCV000115862.20 | |
Benign (2) |
criteria provided, multiple submitters, no conflicts
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Feb 1, 2024 | RCV000119120.16 | |
Benign/Likely benign (7) |
criteria provided, multiple submitters, no conflicts
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Aug 15, 2023 | RCV000212352.29 | |
Benign/Likely benign (5) |
criteria provided, multiple submitters, no conflicts
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Mar 1, 2024 | RCV000679551.36 | |
Likely benign (1) |
criteria provided, single submitter
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Aug 9, 2021 | RCV003149807.9 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Likely benign
(-)
|
criteria provided, single submitter
Method: clinical testing
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NOT SPECIFIED
Affected status: unknown
Allele origin:
germline
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PreventionGenetics, part of Exact Sciences
Accession: SCV000310134.2
First in ClinVar: Oct 02, 2016 Last updated: May 13, 2023 |
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Benign
(Jul 17, 2014)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV000149771.10
First in ClinVar: May 17, 2014 Last updated: Feb 19, 2018 |
Comment:
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at … (more)
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. (less)
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Benign
(Dec 03, 2014)
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criteria provided, single submitter
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV000172889.5
First in ClinVar: Aug 06, 2014 Last updated: Nov 29, 2022 |
Comment:
This alteration is classified as benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA … (more)
This alteration is classified as benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. (less)
Number of individuals with the variant: 1
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Likely benign
(Aug 09, 2021)
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criteria provided, single submitter
Method: clinical testing
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Breast and/or ovarian cancer
Affected status: unknown
Allele origin:
germline
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CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario
Accession: SCV003837765.1
First in ClinVar: Mar 11, 2023 Last updated: Mar 11, 2023 |
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Benign
(Aug 01, 2022)
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criteria provided, single submitter
Method: clinical testing
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Hereditary diffuse gastric adenocarcinoma
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
germline
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European Reference Network on Genetic Tumour Risk Syndromes (ERN-GENTURIS), i3s - Instituto de Investigação e Inovação em Saúde, University of Porto
Study: ERN GENTURIS
Accession: SCV003926665.1 First in ClinVar: Jun 03, 2023 Last updated: Jun 03, 2023 |
Comment:
BA1; BS2 (PMID: 30311375)
Geographic origin: Europe
Comment on evidence:
5 families fulfilling 2020 HDGC criteria; 24 families not fulfilling 2020 HDGC criteria-12 Familial history of breast cancer; 4 Familial history of gastric cancer; 3 … (more)
5 families fulfilling 2020 HDGC criteria; 24 families not fulfilling 2020 HDGC criteria-12 Familial history of breast cancer; 4 Familial history of gastric cancer; 3 Familial history of gastric+breast cancer; 9 Familial history of other cancers than gastric cancer or breast cancer (less)
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Likely benign
(Nov 03, 2021)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: not provided
Allele origin:
germline
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Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden
Accession: SCV002009848.3
First in ClinVar: Nov 06, 2021 Last updated: Jul 16, 2023 |
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Benign
(Aug 15, 2023)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital
Accession: SCV002551753.4
First in ClinVar: Jul 30, 2022 Last updated: Aug 18, 2023 |
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Benign
(Nov 03, 2023)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV001472271.4
First in ClinVar: Jan 26, 2021 Last updated: Feb 20, 2024 |
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Benign
(Feb 01, 2024)
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criteria provided, single submitter
Method: clinical testing
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Hereditary diffuse gastric adenocarcinoma
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000153833.6
First in ClinVar: Jun 03, 2014 Last updated: Feb 28, 2024 |
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Likely benign
(Feb 14, 2017)
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criteria provided, single submitter
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C.
Accession: SCV000576453.1
First in ClinVar: May 29, 2016 Last updated: May 29, 2016 |
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Benign
(Apr 05, 2018)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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Eurofins Ntd Llc (ga)
Accession: SCV000860261.1
First in ClinVar: May 03, 2018 Last updated: May 03, 2018 |
Number of individuals with the variant: 1
Sex: mixed
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Benign
(May 02, 2021)
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criteria provided, single submitter
Method: curation
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Sema4, Sema4
Accession: SCV002529191.1
First in ClinVar: Jun 24, 2022 Last updated: Jun 24, 2022 |
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Likely benign
(Dec 09, 2014)
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criteria provided, single submitter
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Color Diagnostics, LLC DBA Color Health
Accession: SCV000684468.2
First in ClinVar: Feb 19, 2018 Last updated: Dec 11, 2022 |
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Benign
(Mar 01, 2024)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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CeGaT Center for Human Genetics Tuebingen
Accession: SCV001150947.21
First in ClinVar: Feb 03, 2020 Last updated: Apr 15, 2024 |
Comment:
CDH1: BS1, BS2
Number of individuals with the variant: 12
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Benign
(-)
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no assertion criteria provided
Method: clinical testing
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not specified
Affected status: yes
Allele origin:
germline
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Genome Diagnostics Laboratory, Amsterdam University Medical Center
Study: VKGL Data-share Consensus
Accession: SCV001809005.1 First in ClinVar: Aug 25, 2021 Last updated: Aug 25, 2021 |
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Benign
(-)
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no assertion criteria provided
Method: clinical testing
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not specified
Affected status: yes
Allele origin:
germline
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Clinical Genetics, Academic Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001921442.1 First in ClinVar: Sep 24, 2021 Last updated: Sep 24, 2021 |
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Likely benign
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001953605.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021 |
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Likely benign
(-)
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no assertion criteria provided
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
unknown
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Mayo Clinic Laboratories, Mayo Clinic
Accession: SCV000691815.1
First in ClinVar: Feb 19, 2018 Last updated: Feb 19, 2018 |
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Likely benign
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001741428.3 First in ClinVar: Jul 07, 2021 Last updated: Sep 08, 2021 |
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Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Genotype-first approach to identify associations between CDH1 germline variants and cancer phenotypes: a multicentre study by the European Reference Network on Genetic Tumour Risk Syndromes. | Garcia-Pelaez J | The Lancet. Oncology | 2023 | PMID: 36436516 |
Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. | Richards S | Genetics in medicine : official journal of the American College of Medical Genetics | 2015 | PMID: 25741868 |
Identification and characterization of CDH1 germline variants in sporadic gastric cancer patients and in individuals at risk of gastric cancer. | Garziera M | PloS one | 2013 | PMID: 24204729 |
Identification of germline mutations in the cancer predisposing gene CDH1 in patients with orofacial clefts. | Vogelaar IP | Human molecular genetics | 2013 | PMID: 23197654 |
E-cadherin genetic screening and clinico-pathologic characteristics of early onset gastric cancer. | Corso G | European journal of cancer (Oxford, England : 1990) | 2011 | PMID: 21106365 |
Germline mutations of the E-cadherin(CDH1) and TP53 genes, rather than of RUNX3 and HPP1, contribute to genetic predisposition in German gastric cancer patients. | Keller G | Journal of medical genetics | 2004 | PMID: 15173255 |
Identification of CDH1 germline missense mutations associated with functional inactivation of the E-cadherin protein in young gastric cancer probands. | Suriano G | Human molecular genetics | 2003 | PMID: 12588804 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=CDH1 | - | - | - | - |
Text-mined citations for rs200673941 ...
HelpRecord last updated Apr 15, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.