This variant is considered likely benign. Homozygosity has been confirmed in one or more individuals. As homozygosity for pathogenic variants in this gene is generally assumed to result in embryonic lethality, this variant is unlikely to be pathogenic.
ClinVar Genomic variation as it relates to human health
NM_004360.5(CDH1):c.2282_2284del (p.Gly761del)
Germline
Classification
Help
criteria provided, conflicting classifications. Learn more about how ClinVar calculates review status.
Conflicting classifications of pathogenicity
Uncertain significance(7); Likely benign(3)
Uncertain significance(7); Likely benign(3)
10 out of 11 submissions contributed to this classification
Help
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.
11
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_004360.5(CDH1):c.2282_2284del (p.Gly761del)
Variation ID: 239892 Accession: VCV000239892.31
- Type and length
-
Deletion, 3 bp
- Location
-
Cytogenetic: 16q22.1 16: 68828290-68828292 (GRCh38) [ NCBI UCSC ] 16: 68862193-68862195 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
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 Jul 1, 2016 Oct 5, 2025 Jul 8, 2025 - HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_004360.5:c.2282_2284del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_004351.1:p.Gly761del inframe deletion NM_004360.5:c.2282_2284delGAG MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NM_001317184.2:c.2099_2101del NP_001304113.1:p.Gly700del inframe deletion NM_001317185.2:c.734_736del NP_001304114.1:p.Gly245del inframe deletion NM_001317186.2:c.317_319del NP_001304115.1:p.Gly106del inframe deletion NM_004360.3:c.2282_2284del NM_004360.4:c.2282_2284delGAG NC_000016.10:g.68828291_68828293del NC_000016.9:g.68862194_68862196del NG_008021.1:g.96000_96002del LRG_301:g.96000_96002del LRG_301t1:c.2282_2284del - Protein change
- G761del, G106del, G245del, G700del
- Other names
- -
- Canonical SPDI
- NC_000016.10:68828289:GGAG:G
-
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.
- -
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
- -
- Links
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 | ||
|---|---|---|---|---|---|---|
| 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. |
|||
| CDH1 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
4982 | 5080 | |
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. |
|---|---|---|---|---|
| Likely benign (3) |
criteria provided, multiple submitters, no conflicts
|
Nov 12, 2024 | RCV000233310.18 | |
| Uncertain significance (2) |
criteria provided, multiple submitters, no conflicts
|
Oct 19, 2023 | RCV000287743.7 | |
| Conflicting classifications of pathogenicity (3) |
criteria provided, conflicting classifications
|
Jul 8, 2025 | RCV000564966.8 | |
| Uncertain significance (1) |
criteria provided, single submitter
|
Jan 28, 2025 | RCV001194011.4 | |
| Uncertain significance (1) |
criteria provided, single submitter
|
Mar 10, 2022 | RCV005361419.1 | |
| Uncertain significance (1) |
criteria provided, single submitter
|
Feb 19, 2024 | RCV004567739.1 |
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. |
Expand all rows
Collapse all rows
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. |
|
|---|---|---|---|---|---|
|
Likely benign
(Mar 03, 2023)
C
Contributing to aggregate classification
|
criteria provided, single submitter
|
Hereditary diffuse gastric adenocarcinoma |
Myriad Genetics, Inc.
Accession: SCV004019552.1
First in ClinVar: Jul 29, 2023 Last updated: Jul 29, 2023 |
Comment:
show
This variant is considered likely benign. Homozygosity has been confirmed in one or more individuals. As homozygosity for pathogenic variants in this gene is generally assumed to result in embryonic lethality, this variant is unlikely to be pathogenic. (less)
Observation: 1
Collection method: clinical testing
Allele origin: unknown
Affected status: unknown
Observation 1
Collection method: clinical testing
Allele origin: unknown
Affected status: unknown
|
|
|
Uncertain significance
(Oct 19, 2023)
C
Contributing to aggregate classification
|
criteria provided, single submitter
|
Not Provided |
GeneDx
Accession: SCV000329235.7
First in ClinVar: Dec 06, 2016 Last updated: Nov 25, 2023 |
Comment:
show
Not observed at significant frequency in large population cohorts (gnomAD); In-frame deletion of 1 amino acid in a non-repeat region; In silico analysis supports a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 15235021, 22850631) (less)
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: yes
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: yes
|
|
|
Uncertain significance
(Jun 17, 2023)
C
Contributing to aggregate classification
|
criteria provided, single submitter
|
not provided |
Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV001134075.3
First in ClinVar: Jan 05, 2020 Last updated: Jan 06, 2024 |
Comment:
show
This variant has not been reported in the published literature. It also has not been reported in large, multi-ethnic general populations (Genome Aggregation Database, http://gnomad.broadinstitute.org). Based on the available information, we are unable to determine the clinical significance of this variant. (less)
Observation: 1
Collection method: clinical testing
Allele origin: unknown
Affected status: unknown
Observation 1
Collection method: clinical testing
Allele origin: unknown
Affected status: unknown
|
|
|
Uncertain significance
(Feb 19, 2024)
C
Contributing to aggregate classification
|
criteria provided, single submitter
|
Familial cancer of breast |
Baylor Genetics
Accession: SCV005060078.1
First in ClinVar: Jun 17, 2024 Last updated: Jun 17, 2024 |
Observation: 1
Collection method: clinical testing
Allele origin: unknown
Affected status: unknown
Observation 1
Collection method: clinical testing
Allele origin: unknown
Affected status: unknown
|
|
|
Likely benign
(Sep 10, 2024)
C
Contributing to aggregate classification
|
criteria provided, single submitter
|
Hereditary cancer-predisposing syndrome |
Ambry Genetics
Accession: SCV000661627.6
First in ClinVar: Jan 01, 2018 Last updated: Jan 13, 2025 |
Comment:
show
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, 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)
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: unknown
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: unknown
|
|
|
Likely benign
(Nov 12, 2024)
C
Contributing to aggregate classification
|
criteria provided, single submitter
|
Hereditary diffuse gastric adenocarcinoma |
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000288458.12
First in ClinVar: Jul 01, 2016 Last updated: Feb 25, 2025 |
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: unknown
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: unknown
|
|
|
Uncertain significance
(Mar 10, 2022)
C
Contributing to aggregate classification
|
criteria provided, single submitter
|
CDH1-related diffuse gastric and lobular breast cancer syndrome |
Department of Pathology and Laboratory Medicine, Sinai Health System
Accession: SCV005920350.1
First in ClinVar: Apr 28, 2025 Last updated: Apr 28, 2025 |
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: no
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: no
|
|
|
Uncertain significance
(Jun 13, 2024)
C
Contributing to aggregate classification
|
criteria provided, single submitter
|
Hereditary cancer-predisposing syndrome |
Color Diagnostics, LLC DBA Color Health
Accession: SCV006063653.1
First in ClinVar: May 03, 2025 Last updated: May 03, 2025 |
Comment:
show
This variant causes a deletion of glycine at codon 761 of the CDH1 protein. To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with CDH1-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. (less)
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: unknown
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: unknown
Platform type: NGS
|
|
|
Uncertain significance
(Jan 28, 2025)
C
Contributing to aggregate classification
|
criteria provided, single submitter
|
not specified |
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV001363235.4
First in ClinVar: Jun 22, 2020 Last updated: May 25, 2025 |
Comment:
show
Variant summary: CDH1 c.2282_2284delGAG (p.Gly761del) results in an in-frame deletion that is predicted to remove 1 amino acid from the encoded protein. The variant was absent in 251468 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.2282_2284delGAG in individuals affected with CDH1-related conditions and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 239892). Based on the evidence outlined above, the variant was classified as uncertain significance. (less)
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: unknown
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: unknown
|
|
|
Uncertain significance
(Jul 08, 2025)
C
Contributing to aggregate classification
|
criteria provided, single submitter
|
Hereditary cancer-predisposing syndrome |
Laboratorio de I+D, Fundación Centro Médico de Asturias
Additional submitter:
SpadaHC, Centro de Investigación Biomédica en Red Cáncer (CIBERONC)
Accession: SCV006550750.1
First in ClinVar: Oct 05, 2025 Last updated: Oct 05, 2025 |
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: unknown
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: unknown
|
|
|
Uncertain significance
(Aug 02, 2016)
N
Not contributing to aggregate classification
|
no assertion criteria provided
|
Hereditary diffuse gastric adenocarcinoma |
Counsyl
Accession: SCV000489019.3
First in ClinVar: Jul 01, 2016 Last updated: Jun 29, 2025 |
Comment:
show
This submission and the accompanying classification are no longer maintained by the submitter. For more information on current observations and classification, please contact variantquestions@myriad.com. (less)
Observation: 1
Collection method: clinical testing
Allele origin: unknown
Affected status: unknown
Observation 1
Collection method: clinical testing
Allele origin: unknown
Affected status: unknown
|
|
Comment:
Comment:
Not observed at significant frequency in large population cohorts (gnomAD); In-frame deletion of 1 amino acid in a non-repeat region; In silico analysis supports a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 15235021, 22850631)
Comment:
This variant has not been reported in the published literature. It also has not been reported in large, multi-ethnic general populations (Genome Aggregation Database, http://gnomad.broadinstitute.org). Based on the available information, we are unable to determine the clinical significance of this variant.
Comment:
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, 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.
Comment:
This variant causes a deletion of glycine at codon 761 of the CDH1 protein. To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with CDH1-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Comment:
Variant summary: CDH1 c.2282_2284delGAG (p.Gly761del) results in an in-frame deletion that is predicted to remove 1 amino acid from the encoded protein. The variant was absent in 251468 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.2282_2284delGAG in individuals affected with CDH1-related conditions and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 239892). Based on the evidence outlined above, the variant was classified as uncertain significance.
Comment:
PM1+PM4+PM2_Supporting
Comment:
This submission and the accompanying classification are no longer maintained by the submitter. For more information on current observations and classification, please contact variantquestions@myriad.com.
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| https://spadahc.ciberisciii.es/variant/GRCH37/16%2068862193%20GGA/- | - | - | - | - |
Text-mined citations for rs878854683 ...
HelpThese citations are identified by LitVar using
the rs number, so they may include citations for more than one variant
at this location. Please review the LitVar results carefully for your
variant of interest.
Record last updated Oct 12, 2025
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.