About CDH1
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
CDH1 c.2053G>A, p.(Val685Met)
Classification
Likely benign
Variant description:
No variant summary was recorded for this case.
Five-step scale from benign to pathogenic. This variant is likely benign. Select a step to read what it means.
Likely benign.A likely benign classification under the recorded framework.
In plain language
Gene-level background from the recorded interpretation.
Words with a dotted underline have a short definition. Hover or tap them.
LYFE Sciences is an AI system, and it can make mistakes.
Criteria may be applied incorrectly, sources may be misread, and a
confident-looking classification can still be wrong.
Double-check every criterion and its underlying evidence
before relying on any call.
01The reasoning
How it was classified
The recorded framework is ClinGen CDH1 VCEP v3.1.0. The criteria and strengths shown below come from the saved assessment; this page does not recalculate the classification.
Recorded applied criteria
The applied criteria and their strengths are shown as assessed under the stated framework.
Pathogenic evidence criteria: 0
Benign evidence criteria: 2
Pathogenic criteria applied · 0
No pathogenic criterion marked as applied in the recorded assessment.
Benign criteria applied · 2
BP2Supporting
BP2 · supporting
Per CDH1 VCEP BP2_Supporting rule: 'observed in the homozygous state in gnomAD.' gnomAD v4.1 reports 1 homozygote for this variant (total_hom = 1). This meets the VCEP-specified threshold for BP2 at the Supporting benign level. The single homozygote observation in a large population database (1,613,720 alleles) is consistent with a variant unlikely to cause a highly penetrant dominant disorder like HDGC. Note: a single homozygote in gnomAD may represent a technical artifact; the expert panel's Likely benign classification provides orthogonal support.
BP6Supporting
BP6 · supporting
Expert panel Clingen Gastric Cancer Variant Curation Expert Panel classified as Likely benign.
Recorded classification: Likely benign
ClinGen CDH1 Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines Version 3.1 v3.1.0 lacked a usable explicit final combination framework, so generic ACMG/AMP 2015 final-combination rules were applied as fallback; applied criteria: BP2 supporting benign, BP6 supporting benign; combination = 2 supporting benign, which maps to Likely Benign.
02The sources
Evidence at a glance
Evidence summaries and captured source records, where available. Missing entries should not be interpreted as negative findings.
gnomAD v4.1
gnomAD v2.1
Population frequency
24 / 1,613,720 alleles
gnomAD v4.1: 24 / 1,613,720 alleles. Recorded AF 1.48725e-05. Recorded homozygote count 1.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 1.59066e-05; MAF= 0.00159%, 4/251468 alleles, homozygotes = 0) and has highest observed frequency in the African/African American population (AF= 6.15157e-05; MAF= 0.00615%, 1/16256 alleles, homozygotes = 0); grpmax FAF= 9.58e-06.
gnomAD-Canada
This variant is present in gnomAD-Canada v1.0 (AF= 0.00010856584518510477, 2/18422 alleles, homozygotes = 0).
No listed criterion applied
SpliceAI score
0.110 maximum delta
Recorded SpliceAI maximum delta score: 0.110. Refer to the recorded PP3/BP4 rationale for interpretation.
No listed criterion applied
SpliceAI ↗
ClinVar submissions
7 reported laboratory submissions
5 Likely benign · 2 Uncertain significance.
Functional evidence
Statement recorded
OncoKB did not identify variant-specific reviewed functional evidence for this variant; gene-level curated context is available for reviewer follow-up. CDH1 (E-cadherin), a tumor suppressor involved in cell adhesion, is altered by mutation or deletion in various cancer typess, most frequently in breas
No listed criterion applied
OncoKB ↗
COSMIC
Cancer Hotspots
Somatic evidence
1 recorded samples
This variant has previously been reported in somatic cancers (COSMIC; COSV55733838, n = 1 times).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.
Context only
For specialists
Technical detail
ACMG/AMP criteria under ClinGen CDH1 VCEP v3.1.0, with the data and sources behind each one.
26 criteria with recorded statuses: 2 met · 6 not met · 9 not assessed · 9 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
Met
Not met
Not assessed
Not applicable
NM_004360.5:c.2053G>A (p.Val685Met) is a missense variant in CDH1 exon 13. The ClinGen CDH1 Expert Panel has classified this variant as Likely benign (ClinVar Variation ID: 133847).
The variant is present in gnomAD population databases at low frequency: 4/251,468 alleles in v2.1 (AF 0.00159%) and 24/1,613,720 alleles in v4.1 (AF 0.00149%), with one homozygote reported in v4.1. These frequencies exceed the CDH1 VCEP PM2 threshold of ≤1/100,000 alleles, and the homozygote observation meets BP2_Supporting under the VCEP rules.
SpliceAI predicts no significant splicing impact (max delta score 0.11). In silico protein predictors show borderline scores (REVEL 0.47; BayesDel -0.1394), but per CDH1 VCEP, protein-based computational models are not used for PP3/BP4 assessment.
No variant-specific functional studies, segregation data, de novo reports, or case-control studies were identified in the reviewed literature. Six full-text papers and 10 additional abstracts were reviewed; none mention NM_004360.5:c.2053G>A or p.Val685Met.
One homozygote in gnomAD v4.1 meets CDH1 VCEP BP2_Supporting ('observed in the homozygous state in gnomAD'), providing a single line of benign evidence. No other ACMG criteria are met with the available evidence. Most criteria remain unassessed due to lack of variant-specific functional, segregation, or clinical phenotype data.
No criteria match.
Met · 2
BP2 SupportingPer CDH1 VCEP BP2_Supporting rule: 'observed in the homozygous state in gnomAD.' gnomAD v4.1 reports 1 homozygote for this variant (total_hom = 1). This meets the VCEP-specified threshold for BP2 at the Supporting benign level. The single homozygote observation in a large population database (1,613,720 alleles) is consistent with a variant unlikely to cause a highly penetrant dominant disorder like HDGC. Note: a single homozygote in gnomAD may represent a technical artifact; the expert panel's Likely benign classification provides orthogonal support. Details ▾Hide ▴
Evidence considered
- gnomAD v4.1: 1 homozygote (exome)
- ClinGen CDH1 VCEP classification: Likely benign
Still missing
- Single homozygote in gnomAD may be technical artifact
- confirm with orthogonal data
Sources
Not met · 6 · evaluated, threshold not reached
PS4 PS4 requires families meeting HDGC criteria. The ClinGen CDH1 Expert Panel classified this variant as Likely benign, indicating no enrichment in affected individuals versus controls. No published case-control study demonstrates significant enrichment. Population data show the variant at low frequency in gnomAD, inconsistent with a highly penetrant pathogenic variant. Details ▾Hide ▴
Evidence considered
- ClinGen CDH1 VCEP classification: Likely benign
- gnomAD v4.1: 24/1
- 613
- 720 alleles
- 1 homozygote
- No case-control evidence of enrichment in HDGC
Still missing
- No published case-control study comparing variant frequency in HDGC vs controls
Sources
PM2 Per CDH1 VCEP, PM2_Supporting requires ≤1 out of 100,000 alleles in the gnomAD cohort. gnomAD v2.1: 4/251,468 alleles (1.59 per 100,000), exceeding the threshold. gnomAD v4.1: 24/1,613,720 alleles (1.49 per 100,000), also exceeding the threshold. Additionally, in gnomAD v4.1 Admixed American subpopulation: 8/60,000 alleles (13.3 per 100,000), exceeding the subpopulation rule of ≤1 per 50,000 when ≥2 individuals are present. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1: AF 0.00159% (4/251
- 468)
- gnomAD v4.1: AF 0.00149% (24/1
- 613
- 720)
- gnomAD v4.1 Admixed American: AF 0.0133% (8/60
- 000)
Sources
PP3 Per CDH1 VCEP, PP3 is limited to splicing predictions only (do not use protein-based computational models). SpliceAI max delta score is 0.11, which is below the threshold for predicted splicing impact. No additional in silico splicing predictors (MaxEntScan, SSF, GeneSplicer, HSF, TraP, varSEAK) are available in the evidence record. At least three predictors in agreement are required for PP3_Supporting. Criterion not met. Details ▾Hide ▴
Evidence considered
- SpliceAI max delta: 0.11 — no predicted splicing impact
- Only one splicing predictor (SpliceAI) available
- need ≥3 in agreement per VCEP
Still missing
- Additional splicing predictors (MaxEntScan
- SSF
- GeneSplicer
- HSF
- TraP
- varSEAK) not assessed
Sources
BA1 Per CDH1 VCEP, BA1 requires MAF ≥0.2%. gnomAD v2.1 AF: 0.00159% (4/251,468). gnomAD v4.1 AF: 0.00149% (24/1,613,720). Highest subpopulation AF: 0.0133% (Admixed American, gnomAD v4.1). All frequencies are well below the 0.2% BA1 threshold. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1 AF: 0.00159%
- gnomAD v4.1 AF: 0.00149%
- Maximum subpopulation AF: 0.0133% (Admixed American
- v4.1)
Sources
BS1 Per CDH1 VCEP, BS1 requires MAF ≥0.1%. gnomAD v2.1 AF: 0.00159%. gnomAD v4.1 AF: 0.00149%. Highest subpopulation AF: 0.0133% (Admixed American, v4.1). All frequencies are below the 0.1% BS1 threshold. Details ▾Hide ▴
BP4 Per CDH1 VCEP, BP4 is limited to splicing predictions only and requires at least three in silico splicing predictors in agreement (SpliceAI, MaxEntScan, SSF, GeneSplicer, HSF, TraP, varSEAK). Only SpliceAI data is available (max delta 0.11, no splicing impact). A single predictor is insufficient to meet the VCEP requirement of three concordant predictors. Details ▾Hide ▴
Evidence considered
- SpliceAI max delta: 0.11 — no splicing impact
- Only 1 of minimum 3 required predictors available
Still missing
- Additional splicing predictors not assessed
Sources
Not assessed · 9 · no assessment recorded
PS2 No de novo occurrence data identified for this variant. PS2 requires confirmed de novo in a patient meeting HDGC individual phenotype criteria with parental confirmation. No such data found in ClinVar submissions, literature, or other sources. Details ▾Hide ▴
Still missing
- No de novo reports available for this variant
PS3 Per CDH1 VCEP, PS3 requires RNA assay demonstrating abnormal transcripts. This is a missense variant with SpliceAI max delta score of 0.11 (no predicted splicing impact). No variant-specific functional RNA studies identified in the literature. OncoKB reports Unknown Oncogenic Effect with no variant-specific reviewed functional evidence. Details ▾Hide ▴
Evidence considered
- SpliceAI max delta 0.11 — no splicing impact predicted
- OncoKB: Unknown Oncogenic Effect
- no variant-specific functional evidence
Still missing
- No variant-specific functional RNA studies available
Sources
PM6 No assumed de novo occurrences identified. PM6 requires patients meeting HDGC individual phenotype criteria without parental confirmation. No such reports found in ClinVar submissions or literature. Details ▾Hide ▴
Still missing
- No de novo reports (confirmed or unconfirmed) available
PP1 No cosegregation data identified for this variant. PP1 requires informative meioses across families. No published segregation studies found in the literature or ClinVar submissions. Details ▾Hide ▴
Still missing
- No segregation data available
BS2 BS2 requires phenotype data on individuals carrying the variant — specifically, individuals without gastric cancer, diffuse gastric cancer, signet ring cell tumors, or lobular breast cancer, and whose families do not suggest HDGC. gnomAD population data lack individual-level phenotype information. gnomAD v4.1 contains 24 heterozygous individuals and 1 homozygote, but the clinical status of these individuals is unknown. Cannot apply BS2 without phenotype data. Details ▾Hide ▴
Evidence considered
- gnomAD v4.1: 24 heterozygotes
- 1 homozygote — phenotype data unavailable
Still missing
- Phenotype data unavailable for gnomAD carriers
Sources
BS3 Per CDH1 VCEP, BS3 requires functional RNA studies demonstrating no impact on transcript composition and is limited to synonymous, intronic, or non-coding variants. This is a missense variant. No variant-specific functional benign studies identified in the literature. Details ▾Hide ▴
Evidence considered
- Missense variant
- VCEP BS3 is restricted to synonymous/intronic/non-coding
Still missing
- No variant-specific functional RNA studies available
BS4 No segregation data available for this variant. BS4 requires lack of segregation in affected family members. No published family studies identified in the literature or ClinVar submissions. Details ▾Hide ▴
Still missing
- No segregation data available
BP5 BP5 requires identification of a pathogenic/likely pathogenic variant in an alternate gene known to cause HDGC (per VCEP: currently only CTNNA1). No data on alternate molecular diagnoses available for individuals carrying this variant. Details ▾Hide ▴
Still missing
- No data on alternate molecular diagnoses in variant carriers
PS5 No alternative nucleotide change at c.2053 has been reported as pathogenic. No comparator data available to assess whether a different substitution at the same position is established as pathogenic. Details ▾Hide ▴
Still missing
- No known pathogenic alternative at c.2053
Not applicable · 9· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/APVS1 applies to null variants (nonsense, frameshift, canonical splice sites). NM_004360.5:c.2053G>A is a missense variant (p.Val685Met) in exon 13 and does not fall into any PVS1 null-variant bucket. The CDH1 VCEP PVS1 decision tree is not applicable to missense substitutions. Details ▾Hide ▴
Evidence considered
- Missense substitution at c.2053G>A
- variant class: other
- not a null variant
Sources
pvs1_variant_assessmentpvs1_gene_context
PS1 VCEPPS1 is marked Not Applicable for this VCEP per the ClinGen CDH1 Expert Panel Specifications v3.1.0. Details ▾Hide ▴
PM1 VCEPPM1 is marked Not Applicable for this VCEP per the ClinGen CDH1 Expert Panel Specifications v3.1.0. Details ▾Hide ▴
PM5 N/APer CDH1 VCEP v3.1.0, PM5 is repurposed for nonsense and frameshift variants predicted/proven to undergo NMD or located upstream of the last known pathogenic truncating variant (c.2506G>T, p.Glu836Ter). This is a missense variant and does not qualify for VCEP-specified PM5_Supporting. Classic same-residue missense PM5 is not applied under this VCEP. Details ▾Hide ▴
Evidence considered
- CDH1 VCEP restricts PM5 to nonsense/frameshift variants
- pm5_candidates confirms not eligible for classic PM5
Sources
cspec ↗pm5_candidates
PP2 VCEPPP2 is marked Not Applicable for this VCEP per the ClinGen CDH1 Expert Panel Specifications v3.1.0. Details ▾Hide ▴
PP4 VCEPPP4 is marked Not Applicable for this VCEP per the ClinGen CDH1 Expert Panel Specifications v3.1.0. Details ▾Hide ▴
PP5 VCEPPP5 is marked Not Applicable for this VCEP per the ClinGen CDH1 Expert Panel Specifications v3.1.0. This criterion is not for use as recommended by the ClinGen Sequence Variant Interpretation VCEP Review Committee. Details ▾Hide ▴
BP1 VCEPBP1 is marked Not Applicable for this VCEP per the ClinGen CDH1 Expert Panel Specifications v3.1.0. Details ▾Hide ▴
BP7 N/APer CDH1 VCEP, BP7 applies to synonymous and intronic variants at or beyond +7 to -21 positions. NM_004360.5:c.2053G>A is a missense variant (p.Val685Met) in exon 13. BP7 is not applicable to missense substitutions. Details ▾Hide ▴
Identifiers
- Gene
- CDH1
- Transcript
- NM_004360.5
- Coding (HGVS c.)
- NM_004360.5:c.2053G>A
- Protein (HGVS p.)
- NP_004351.1:p.(Val685Met)
- GRCh38
- chr16:68823515 G>A
- GRCh37
- chr16:68857418 G>A
- ClinVar
- 925393, 133847
- COSMIC
- COSV55733838
Gene diagram
Every interpreted variant in CDH1, mapped onto the exon structure of NM_004360.5. Select a row to find it on the plot.
CDH1NM_004360.5
Fetching transcript structure from UCSC…
Exons
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Transcript span
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Strand
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Variants mapped
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Source
UCSC ncbiRefSeqCurated
All variants in CDH1
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Select a row to find it on the plot; use the link to open its page.
| Protein | Location | Classification | Link |
|---|
gnomAD v4.1
24 / 1,613,720 alleles
AF 1.49e-05 · 1 homozygotes · FAF 6.61e-05
gnomAD v2.1
4 / 251,468 alleles
AF 1.59e-05 · 0 homozygotes · FAF 9.58e-06
gnomAD-Canada v1.0
Allele count data not recorded
By genetic ancestry
gnomAD v4.1
AF 1.5e-05 · 24 / 1,613,720 alleles · 1 hom · FAF 6.6e-05
| Admixed American8 / 60,000 | 0.00013 |
| East Asian2 / 44,886 | 4.5e-05 |
| African/African American3 / 75,016 | 4e-051 hom |
| South Asian2 / 91,070 | 2.2e-05 |
| Remaining individuals1 / 62,494 | 1.6e-05 |
| European (non-Finnish)8 / 1,179,670 | 6.8e-06 |
0 alternate alleles recorded in 4 other groups: European (Finnish), Amish, Middle Eastern, Ashkenazi Jewish.
gnomAD v2.1
AF 1.6e-05 · 4 / 251,468 alleles · 0 hom · FAF 9.6e-06
| African/African American1 / 16,256 | 6.2e-05 |
| Admixed American2 / 34,592 | 5.8e-05 |
| East Asian1 / 18,394 | 5.4e-05 |
0 alternate alleles recorded in 5 other groups: Ashkenazi Jewish, European (Finnish), European (non-Finnish), Remaining individuals, South Asian.
gnomAD-Canada
AF not recorded · ? / ? alleles
Statements
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 1.48725e-05; MAF= 0.00149%, 24/1613720 alleles, homozygotes = 1) and has highest observed frequency in the Admixed American population (AF= 0.000133333; MAF= 0.01333%, 8/60000 alleles, homozygotes = 0); grpmax FAF= 6.615e-05.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 1.59066e-05; MAF= 0.00159%, 4/251468 alleles, homozygotes = 0) and has highest observed frequency in the African/African American population (AF= 6.15157e-05; MAF= 0.00615%, 1/16256 alleles, homozygotes = 0); grpmax FAF= 9.58e-06.
gnomAD-Canada
This variant is present in gnomAD-Canada v1.0 (AF= 0.00010856584518510477, 2/18422 alleles, homozygotes = 0).
SpliceAI and Pangolin
Other predictors
- REVEL
- 0.470
- BayesDel
- -0.139
How the predictions were used
PP3 Per CDH1 VCEP, PP3 is limited to splicing predictions only (do not use protein-based computational models). SpliceAI max delta score is 0.11, which is below the threshold for predicted splicing impact. No additional in silico splicing predictors (MaxEntScan, SSF, GeneSplicer, HSF, TraP, varSEAK) are available in the evidence record. At least three predictors in agreement are required for PP3_Supporting. Criterion not met. Details ▾Hide ▴
Evidence considered
- SpliceAI max delta: 0.11 — no predicted splicing impact
- Only one splicing predictor (SpliceAI) available
- need ≥3 in agreement per VCEP
Still missing
- Additional splicing predictors (MaxEntScan
- SSF
- GeneSplicer
- HSF
- TraP
- varSEAK) not assessed
Sources
BP4 Per CDH1 VCEP, BP4 is limited to splicing predictions only and requires at least three in silico splicing predictors in agreement (SpliceAI, MaxEntScan, SSF, GeneSplicer, HSF, TraP, varSEAK). Only SpliceAI data is available (max delta 0.11, no splicing impact). A single predictor is insufficient to meet the VCEP requirement of three concordant predictors. Details ▾Hide ▴
Evidence considered
- SpliceAI max delta: 0.11 — no splicing impact
- Only 1 of minimum 3 required predictors available
Still missing
- Additional splicing predictors not assessed
Sources
BP7 N/APer CDH1 VCEP, BP7 applies to synonymous and intronic variants at or beyond +7 to -21 positions. NM_004360.5:c.2053G>A is a missense variant (p.Val685Met) in exon 13. BP7 is not applicable to missense substitutions. Details ▾Hide ▴
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.11). REVEL score = 0.47. BayesDel score = -0.1394.
9 paper records listed. No publication is explicitly linked to an applied criterion in the recorded metadata. None of the listed paper records explicitly indicates that the variant is named.
Recorded publications
-
PMID 25741868 ↗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.ACMG/AMP standards and guidelines for sequence variant interpretation. This is a consensus methods paper describing the variant classification framework; NM_004360.5:c.2053G>A is not mentioned.Does not name this variant
-
PMID 26467025 ↗A Standardized DNA Variant Scoring System for Pathogenicity Assessments in Mendelian Disorders.Standardized DNA variant scoring system (Sherloc precursor) for pathogenicity assessments in Mendelian disorders. NM_004360.5:c.2053G>A was not identified in the text.Does not name this variant
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PMID 29936259 ↗Analytical Validation of a Hybrid Capture-Based Next-Generation Sequencing Clinical Assay for Genomic Profiling of Cell-Free Circulating Tumor DNA.Clark TA et al. · 2018Analytical validation of a hybrid capture-based NGS clinical assay for genomic profiling of cell-free circulating tumor DNA. NM_004360.5:c.2053G>A was not identified in the text.Does not name this variant
-
PMID 31925297 ↗Diversity spectrum analysis identifies mutation-specific effects of cancer driver genes.Dong X et al. · 2020Diversity spectrum analysis for mutation-specific effects of cancer driver genes using a network-based computational framework. NM_004360.5:c.2053G>A was not identified in the text.Does not name this variant
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PMID 17392385 ↗American Cancer Society guidelines for breast screening with MRI as an adjunct to mammography.American Cancer Society guidelines for breast screening with MRI. This is a screening guideline paper; NM_004360.5:c.2053G>A was not identified in the abstract.Does not name this variant
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PMID 20065170 ↗American Society of Clinical Oncology policy statement update: genetic and genomic testing for cancer susceptibility.ASCO policy statement on genetic and genomic testing for cancer susceptibility. Discusses general principles of cancer genetic testing. NM_004360.5:c.2053G>A was not identified in the text.Does not name this variant
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PMID 24728327 ↗Germline variation in cancer-susceptibility genes in a healthy, ancestrally diverse cohort: implications for individual genome sequencing.Bodian DL et al. · 2014Germline variation in cancer-susceptibility genes in a healthy ancestrally diverse cohort. Reports population frequency data for cancer predisposition genes but NM_004360.5:c.2053G>A was not identified in the text.Does not name this variant
-
PMID 26324357 ↗American Society of Clinical Oncology Policy Statement Update: Genetic and Genomic Testing for Cancer Susceptibility.ASCO policy statement update on genetic and genomic testing for cancer susceptibility. NM_004360.5:c.2053G>A was not identified in the abstract.Does not name this variant
-
PMID 28492532 ↗Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria. This is a methods paper describing a variant classification framework. NM_004360.5:c.2053G>A was not identified in available content.Does not name this variant
Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.
gnomAD v4.1
24 / 1,613,720 recorded alleles
Open source ↗
gnomAD v2.1
Captured gnomAD v2.1 source record
Open source ↗
SpliceAI Lookup
Recorded maximum delta 0.110
Open source ↗
ClinVar
5 Likely benign · 2 Uncertain significance
Open source ↗
COSMIC
Captured COSMIC source record
Open source ↗
Cancer hotspots
Captured Cancer Hotspots source record
Open source ↗
OncoKB
Captured OncoKB source record
Open source ↗
ClinGen CSpec
Captured ClinGen CSpec source record
Open source ↗
All source links
- ClinGen CSpec ↗cspec.genome.network/cspec/ui/svi/doc/135637579
- ClinVar ↗www.ncbi.nlm.nih.gov/clinvar/variation/133847/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/16-68857418-G-A?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr16-68823515-G-A?dataset=gn…
- gnomAD-Canada ↗http://192.168.4.76:8001/variant/16-68823515-G-A
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_004360.5%3Ac.2053…
- OncoKB ↗www.oncokb.org/gene/CDH1/V685M
- COSMIC ↗cancer.sanger.ac.uk/cosmic/mutation/overview?id=121133873
- Cancer hotspots ↗www.cancerhotspots.org/
Statements for reports
The evidence statements recorded by the interpretation pipeline. They have not been reinterpreted by the page.
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 1.48725e-05; MAF= 0.00149%, 24/1613720 alleles, homozygotes = 1) and has highest observed frequency in the Admixed American population (AF= 0.000133333; MAF= 0.01333%, 8/60000 alleles, homozygotes = 0); grpmax FAF= 6.615e-05.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 1.59066e-05; MAF= 0.00159%, 4/251468 alleles, homozygotes = 0) and has highest observed frequency in the African/African American population (AF= 6.15157e-05; MAF= 0.00615%, 1/16256 alleles, homozygotes = 0); grpmax FAF= 9.58e-06.
gnomAD-Canada
This variant is present in gnomAD-Canada v1.0 (AF= 0.00010856584518510477, 2/18422 alleles, homozygotes = 0).
ClinVar
This variant has been reported in ClinVar as Likely benign (5 clinical laboratories) and as Uncertain significance (2 clinical laboratories) and as Likely benign by Clingen Gastric Cancer Variant Curation Expert Panel (expert panel). (ClinVarID = 133847)
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.11). REVEL score = 0.47. BayesDel score = -0.1394.
Functional
OncoKB did not identify variant-specific reviewed functional evidence for this variant; gene-level curated context is available for reviewer follow-up. CDH1 (E-cadherin), a tumor suppressor involved in cell adhesion, is altered by mutation or deletion in various cancer typess, most frequently in breas
Somatic
This variant does not lie in a statistically significant hotspot. This variant has previously been reported in somatic cancers (COSMIC; COSV55733838, n = 1 times).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.