About CDH1
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
CDH1 c.48+7C>T, p.?
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. 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
BS3Strong
BS3 · strong
Functional RNA studies (Garziera et al. 2013, PMID 24204729) demonstrated no impact on CDH1 transcript composition for NM_004360.5:c.48+7C>T. RT-PCR of exons 1-5 from peripheral blood mononuclear cells of the variant carrier produced a normal-sized 768 bp fragment identical to wild-type controls. Bidirectional sequencing confirmed the absence of aberrant transcripts. No protein truncations or frameshifts were detected. Per CDH1 VCEP BS3 rule: 'Functional RNA studies demonstrating no impact on transcript composition' applies at Strong strength.
BP7Supporting
BP7 · supporting
NM_004360.5:c.48+7C>T is an intronic variant located at the +7 position of intron 1. Per CDH1 VCEP BP7 rule: 'Synonymous and intronic variants at or beyond +7 to -21 locations.' The variant at +7 falls exactly at the boundary of this rule. The CSPEC instructions note that the CDH1 rule specification does not require a conservation prediction and that BP7 may be used with BP4 to classify variants meeting both criteria as likely benign. Here BP7 is applied independently based on the positional rule.
Recorded classification: Likely benign
ClinGen CDH1 Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines Version 3.1 v3.1 lacked a usable explicit final combination framework, so generic ACMG/AMP 2015 final-combination rules were applied as fallback; applied criteria: BS3 strong benign, BP7 supporting benign; combination = 1 strong benign + 1 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
11 / 1,536,836 alleles
gnomAD v4.1: 11 / 1,536,836 alleles. Recorded AF 7.15756e-06. Recorded homozygote count 0.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 1.52693e-05; MAF= 0.00153%, 2/130982 alleles, homozygotes = 0) and has highest observed frequency in the Remaining individuals population (AF= 0.000250125; MAF= 0.02501%, 1/3998 alleles, homozygotes = 0).
gnomAD-Canada
Not available in gnomAD-Canada v1.0.
No listed criterion applied
SpliceAI score
0.020 maximum delta
Recorded SpliceAI maximum delta score: 0.020. Refer to the recorded PP3/BP4 rationale for interpretation.
ClinVar submissions
4 reported laboratory submissions
4 Likely benign. ClinVar API review status: criteria provided, multiple submitters, no conflicts.
Context only
ClinVar ↗
No screenshot for this evidence
Functional evidence
Not recorded
No standalone functional evidence summary is recorded in evidence_summary.functional.
Somatic evidence
1 recorded samples
This variant has previously been reported in somatic cancers (COSMIC; COSV105066453, n = 1 times).
Context only
COSMIC ↗
For specialists
Technical detail
ACMG/AMP criteria under ClinGen CDH1 VCEP v3.1, with the data and sources behind each one.
26 criteria with recorded statuses: 2 met · 7 not met · 8 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.48+7C>T is an intronic variant at position +7 of intron 1 in CDH1. It has been reported in ClinVar as Likely benign by four clinical laboratories (ClinVar ID 142318, 1-star review status).
This variant is present at very low frequency in gnomAD population databases: 2 of 130,982 alleles in v2.1 (0.00153%) and 11 of 1,536,836 alleles in v4.1 (0.00072%), with no homozygotes observed.
Functional RNA studies by Garziera et al. (2013, PMID 24204729) evaluated the splicing impact of c.48+7C>T using RT-PCR on peripheral blood mononuclear cells from a heterozygous carrier. The transcript was normal in size and sequence compared to wild-type controls, with no aberrant splicing products, protein truncations, or frameshifts detected. These findings satisfy BS3 at strong strength per CDH1 VCEP specifications.
The variant's intronic position at +7 meets the CDH1 VCEP BP7 rule for intronic variants at or beyond the +7 position, providing supporting evidence for a benign interpretation.
SpliceAI predicts no significant splice impact (max delta score = 0.02), consistent with the normal transcript observed in functional RNA studies.
PS3 is not met because the functional data demonstrated no abnormal transcripts; the evidence direction is benign rather than pathogenic.
No criteria match.
Met · 2
BS3 StrongFunctional RNA studies (Garziera et al. 2013, PMID 24204729) demonstrated no impact on CDH1 transcript composition for NM_004360.5:c.48+7C>T. RT-PCR of exons 1-5 from peripheral blood mononuclear cells of the variant carrier produced a normal-sized 768 bp fragment identical to wild-type controls. Bidirectional sequencing confirmed the absence of aberrant transcripts. No protein truncations or frameshifts were detected. Per CDH1 VCEP BS3 rule: 'Functional RNA studies demonstrating no impact on transcript composition' applies at Strong strength. Details ▾Hide ▴
Evidence considered
- RT-PCR of exons 1-5 from PBMCs of c.48+7C>T carrier showed normal transcript (Figure 3A of PMID 24204729)
- Bidirectional sequencing confirmed no aberrant splicing products
- No frameshifts or protein truncations detected
Sources
BP7 SupportingNM_004360.5:c.48+7C>T is an intronic variant located at the +7 position of intron 1. Per CDH1 VCEP BP7 rule: 'Synonymous and intronic variants at or beyond +7 to -21 locations.' The variant at +7 falls exactly at the boundary of this rule. The CSPEC instructions note that the CDH1 rule specification does not require a conservation prediction and that BP7 may be used with BP4 to classify variants meeting both criteria as likely benign. Here BP7 is applied independently based on the positional rule. Details ▾Hide ▴
Evidence considered
- Variant is intronic at position c.48+7
- which is at the +7 boundary defined by the CDH1 VCEP BP7 rule: 'intronic variants at or beyond +7 to -21 locations'
Sources
Not met · 7 · evaluated, threshold not reached
PS3 The only available functional data for this variant (Garziera et al. 2013, PMID 24204729) demonstrated normal CDH1 transcript composition by RT-PCR with no aberrant splicing or protein truncations. Per CDH1 VCEP, PS3 requires RNA assay demonstrating abnormal out-of-frame or in-frame transcripts. The experimental evidence showed no splicing defect, which is contrary to what PS3 requires. Details ▾Hide ▴
Evidence considered
- RT-PCR of exons 1-5 from PBMCs of the c.48+7C>T carrier showed a normal 768 bp band identical to controls (Figure 3A)
- Bidirectional sequencing confirmed no differences from wild-type transcript
- No protein truncations or frameshifts were detected
Sources
PM2 Per CDH1 VCEP PM2 rule: variant must be present at ≤1 per 100,000 alleles in gnomAD. In gnomAD v4.1, the variant is present at 7.16e-06 (11/1,536,836), meeting the total cohort threshold. However, the variant is present in ≥2 individuals within the Remaining subpopulation (2/59,902 = 3.34e-05), which exceeds the required ≤1 per 50,000 (2e-05) subpopulation threshold. In gnomAD v2.1, the variant is present at 1.53e-05 (2/130,982), exceeding the ≤1 per 100,000 total threshold. PM2 is not met in either gnomAD version. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1: 2/130
- 982 = 1.53e-05 total AF (exceeds ≤1/100
- 000 threshold)
- gnomAD v4.1: 11/1
- 536
- 836 = 7.16e-06 total AF (meets ≤1/100
- 000)
- but subpopulation Remaining: 2/59
- 902 = 3.34e-05 (exceeds ≤1/50
- 000 threshold for ≥2 subpopulation alleles)
Sources
PP3 SpliceAI predicts no significant splice impact (max delta = 0.02). The only available functional RNA data (PMID 24204729) confirmed no aberrant splicing. Only one in silico splicing predictor (SpliceAI) is available in the evidence packet; the CDH1 VCEP requires at least three in silico splicing predictors in agreement for supporting strength. No well-characterized pathogenic variant at the same splice site exists to support moderate strength. PP3 is not met. Details ▾Hide ▴
Evidence considered
- SpliceAI max delta = 0.02 (no predicted splice impact)
- RT-PCR from PMID 24204729 confirmed no aberrant splicing
- Insufficient number of in silico predictors for PP3_supporting (only 1 available)
Still missing
- Only 1 of the 7 listed in silico splicing predictors (SpliceAI) is available in the evidence packet
Sources
BA1 The CDH1 VCEP BA1 threshold is an allele frequency greater than 0.2% (MAF > 0.002). In gnomAD v4.1, the global allele frequency is 7.16e-06 (0.00072%), well below 0.2%. In gnomAD v2.1, the global AF is 1.53e-05 (0.00153%), also well below 0.2%. The variant is too rare to meet BA1. Details ▾Hide ▴
Evidence considered
- gnomAD v4.1 total AF = 7.16e-06 (0.00072%) — well below 0.2% threshold
- gnomAD v2.1 total AF = 1.53e-05 (0.00153%) — well below 0.2% threshold
Sources
BS1 The CDH1 VCEP BS1 threshold is an allele frequency greater than 0.1% (MAF > 0.001). In gnomAD v4.1, the global allele frequency is 7.16e-06 (0.00072%), well below 0.1%. In gnomAD v2.1, the global AF is 1.53e-05 (0.00153%), also well below 0.1%. The variant is too rare to meet BS1. Details ▾Hide ▴
Evidence considered
- gnomAD v4.1 total AF = 7.16e-06 (0.00072%) — well below 0.1% threshold
- gnomAD v2.1 total AF = 1.53e-05 (0.00153%) — well below 0.1% threshold
Sources
BP4 The CDH1 VCEP BP4 rule requires at least three in silico splicing predictors in agreement showing no impact. Only SpliceAI is available in the evidence packet (max delta = 0.02, no predicted splice impact). Although the available predictor supports no splicing effect and the functional RNA data (PMID 24204729) confirms this, the VCEP rule strictly requires ≥3 predictors. Without additional predictors (MaxEntScan, SSF, GeneSplicer, HSF, TraP, varSEAK), BP4 cannot be applied. Details ▾Hide ▴
Evidence considered
- SpliceAI max delta = 0.02 (no predicted splice impact)
- Only 1 of 7 listed splicing predictors available — insufficient for BP4 threshold of ≥3
Still missing
- Need at least 2 more in silico splicing predictors (MaxEntScan
- SSF
- GeneSplicer
- HSF
- TraP
- or varSEAK) to reach the ≥3 threshold
Sources
BP5 Per CDH1 VCEP, BP5 applies when a pathogenic/likely pathogenic variant is identified in an alternate gene known to cause HDGC (currently only CTNNA1). No evidence of an alternate molecular basis for disease was identified in the case materials. BP5 is not met. Details ▾Hide ▴
Evidence considered
- No alternate gene P/LP variant (e.g.
- CTNNA1) reported in the case evidence
Not assessed · 8 · no assessment recorded
PS2 No de novo data (with confirmed maternity and paternity) available for NM_004360.5:c.48+7C>T. None of the reviewed publications report de novo occurrence of this variant in a patient meeting HDGC phenotype criteria. Details ▾Hide ▴
Still missing
- No de novo reports identified in literature or ClinVar submissions
PS4 No case-family data available indicating that individuals or families harboring NM_004360.5:c.48+7C>T meet HDGC criteria. The variant was identified in a single AMAG patient without gastric cancer (PMID 24204729), not in HDGC families. Details ▾Hide ▴
Evidence considered
- Variant found in 1 AMAG patient
- not in gastric cancer patients or HDGC families
Still missing
- No HDGC family data available for this variant
Sources
PM6 No assumed de novo (without parental confirmation) data available for NM_004360.5:c.48+7C>T. None of the reviewed publications report de novo occurrence of this variant in a patient meeting HDGC phenotype criteria. Details ▾Hide ▴
Still missing
- No de novo reports identified
PP1 No co-segregation data available for NM_004360.5:c.48+7C>T. No family studies with informative meioses were identified in the literature. Details ▾Hide ▴
Still missing
- No segregation data available
BS2 Insufficient clinical phenotype data to determine whether the 11 individuals in gnomAD v4 (or 2 in gnomAD v2) are free of gastric cancer, diffuse gastric cancer, signet ring cell tumors, or lobular breast cancer, and whether their families lack features suggestive of HDGC. The one individual carrying this variant described in PMID 24204729 was an autoimmune metaplastic atrophic gastritis patient without gastric cancer, but a single observation is insufficient to meet the ≥3 (supporting) or ≥10 (strong) threshold. Details ▾Hide ▴
Evidence considered
- gnomAD individuals lack clinical phenotype annotation for HDGC exclusion
- One AMAG patient without GC reported in PMID 24204729 — below the ≥3 threshold for BS2_supporting
Still missing
- No clinically phenotyped control cohort data confirming absence of GC/DGC/LBC/SRC in variant carriers
- Only 1 carrier with documented absence of GC
- insufficient for BS2
Sources
BS4 No segregation data available for NM_004360.5:c.48+7C>T. Lack of segregation in affected family members cannot be evaluated without family studies. Details ▾Hide ▴
Still missing
- No family segregation data available
BP2 No evidence of NM_004360.5:c.48+7C>T observed in trans with a known pathogenic CDH1 variant (phase confirmed), nor observed in the homozygous state in an individual without personal/family history of DGC, LBC, or SRC tumors. Not observed in the homozygous state in gnomAD. Insufficient data to assess BP2. Details ▾Hide ▴
Evidence considered
- Homozygote count = 0 in gnomAD v2.1 and v4.1
- No co-occurrence data with known pathogenic variants available
Still missing
- No phase or co-occurrence data with pathogenic CDH1 variants
Sources
PS5 PS5 is not a recognized ACMG/AMP 2015 criterion. It does not appear in standard ACMG/AMP guidelines nor in the ClinGen CDH1 VCEP specification. No assessment performed. Details ▾Hide ▴
No further detail was recorded.
Not applicable · 9· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/ANM_004360.5:c.48+7C>T is an intronic variant at the +7 position of intron 1. This is not a canonical ±1,2 splice site variant and does not fall into the CDH1 VCEP PVS1 decision tree for null variants. Per PVS1 variant assessment, this variant is classified in the 'other' bucket with no canonical splice consensus disruption. Details ▾Hide ▴
Evidence considered
- Variant is intronic at position +7
- outside the canonical ±1
- 2 splice consensus
- CDH1 VCEP PVS1 rules apply to null variants and canonical splice sites
- this variant does not qualify
Sources
pvs1_variant_assessmentpvs1_gene_context
PS1 VCEPPS1 is designated as Not Applicable by the ClinGen CDH1 Expert Panel Specification Version 3.1. Details ▾Hide ▴
Evidence considered
- CDH1 CSPEC VCEP v3.1 explicitly marks PS1 as not applicable for this gene
Sources
PM1 VCEPPM1 is designated as Not Applicable by the ClinGen CDH1 Expert Panel Specification Version 3.1. Details ▾Hide ▴
Evidence considered
- CDH1 CSPEC VCEP v3.1 explicitly marks PM1 as not applicable for this gene
Sources
PM5 N/AThe CDH1 VCEP repurposes PM5 for nonsense and frameshift variants predicted/proven to undergo NMD or located upstream of the last known pathogenic truncating variant. NM_004360.5:c.48+7C>T is an intronic substitution, not a nonsense or frameshift variant. PM5 candidate search confirmed not applicable. Details ▾Hide ▴
Evidence considered
- Variant is intronic substitution
- not a nonsense or frameshift variant
- CDH1 VCEP PM5 specification applies only to PTC/truncating variants
Sources
pm5_candidatescspec ↗
PP2 VCEPPP2 is designated as Not Applicable by the ClinGen CDH1 Expert Panel Specification Version 3.1. Details ▾Hide ▴
Evidence considered
- CDH1 CSPEC VCEP v3.1 explicitly marks PP2 as not applicable for this gene
Sources
PP4 VCEPPP4 is designated as Not Applicable by the ClinGen CDH1 Expert Panel Specification Version 3.1. Details ▾Hide ▴
Evidence considered
- CDH1 CSPEC VCEP v3.1 explicitly marks PP4 as not applicable for this gene
Sources
PP5 VCEPPP5 is designated as Not Applicable by the ClinGen CDH1 Expert Panel Specification Version 3.1. The ClinVar entry for this variant (VCV000142318) has a 1-star review status (criteria provided, single submitter), which does not meet the 3-star expert panel threshold for the global PP5/BP6 override rule. Details ▾Hide ▴
BP1 VCEPBP1 is designated as Not Applicable by the ClinGen CDH1 Expert Panel Specification Version 3.1. Additionally, this is an intronic variant, not a missense variant. Details ▾Hide ▴
Evidence considered
- CDH1 CSPEC VCEP v3.1 explicitly marks BP1 as not applicable for this gene
Sources
BP6 VCEPBP6 is designated as Not Applicable by the ClinGen CDH1 Expert Panel Specification Version 3.1. The ClinVar entry for this variant (VCV000142318) has a 1-star review status (criteria provided, single submitter), which does not meet the 3-star expert panel threshold for the global PP5/BP6 override rule. Details ▾Hide ▴
Identifiers
- Gene
- CDH1
- Transcript
- NM_004360.5
- Coding (HGVS c.)
- NM_004360.5:c.48+7C>T
- Protein (HGVS p.)
- NP_004351.1:p.?
- GRCh38
- chr16:68737470 C>T
- GRCh37
- chr16:68771373 C>T
- ClinVar
- 142318
- COSMIC
- COSV105066453
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
11 / 1,536,836 alleles
AF 7.16e-06 · 0 homozygotes · FAF 3.69e-06
gnomAD v2.1
2 / 130,982 alleles
AF 1.53e-05 · 0 homozygotes
gnomAD-Canada v1.0
Allele count data not recorded
By genetic ancestry
gnomAD v4.1
AF 7.2e-06 · 11 / 1,536,836 alleles · 0 hom · FAF 3.7e-06
| Remaining individuals2 / 59,902 | 3.3e-05 |
| European (non-Finnish)9 / 1,148,198 | 7.8e-06 |
0 alternate alleles recorded in 8 other groups: Admixed American, European (Finnish), Amish, East Asian, Middle Eastern, South Asian, Ashkenazi Jewish, African/African American.
gnomAD v2.1
AF 1.5e-05 · 2 / 130,982 alleles · 0 hom
| Remaining individuals1 / 3,998 | 0.00025 |
| East Asian1 / 10,508 | 9.5e-05 |
0 alternate alleles recorded in 6 other groups: African/African American, Admixed American, Ashkenazi Jewish, European (Finnish), European (non-Finnish), South Asian.
Statements
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 7.15756e-06; MAF= 0.00072%, 11/1536836 alleles, homozygotes = 0) and has highest observed frequency in the Remaining individuals population (AF= 3.33879e-05; MAF= 0.00334%, 2/59902 alleles, homozygotes = 0); grpmax FAF= 3.69e-06.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 1.52693e-05; MAF= 0.00153%, 2/130982 alleles, homozygotes = 0) and has highest observed frequency in the Remaining individuals population (AF= 0.000250125; MAF= 0.02501%, 1/3998 alleles, homozygotes = 0).
gnomAD-Canada
Not available in gnomAD-Canada v1.0.
SpliceAI and Pangolin
Other predictors
- REVEL
- Not available
- BayesDel
- Not available
How the predictions were used
BP7 SupportingNM_004360.5:c.48+7C>T is an intronic variant located at the +7 position of intron 1. Per CDH1 VCEP BP7 rule: 'Synonymous and intronic variants at or beyond +7 to -21 locations.' The variant at +7 falls exactly at the boundary of this rule. The CSPEC instructions note that the CDH1 rule specification does not require a conservation prediction and that BP7 may be used with BP4 to classify variants meeting both criteria as likely benign. Here BP7 is applied independently based on the positional rule. Details ▾Hide ▴
Evidence considered
- Variant is intronic at position c.48+7
- which is at the +7 boundary defined by the CDH1 VCEP BP7 rule: 'intronic variants at or beyond +7 to -21 locations'
Sources
PP3 SpliceAI predicts no significant splice impact (max delta = 0.02). The only available functional RNA data (PMID 24204729) confirmed no aberrant splicing. Only one in silico splicing predictor (SpliceAI) is available in the evidence packet; the CDH1 VCEP requires at least three in silico splicing predictors in agreement for supporting strength. No well-characterized pathogenic variant at the same splice site exists to support moderate strength. PP3 is not met. Details ▾Hide ▴
Evidence considered
- SpliceAI max delta = 0.02 (no predicted splice impact)
- RT-PCR from PMID 24204729 confirmed no aberrant splicing
- Insufficient number of in silico predictors for PP3_supporting (only 1 available)
Still missing
- Only 1 of the 7 listed in silico splicing predictors (SpliceAI) is available in the evidence packet
Sources
BP4 The CDH1 VCEP BP4 rule requires at least three in silico splicing predictors in agreement showing no impact. Only SpliceAI is available in the evidence packet (max delta = 0.02, no predicted splice impact). Although the available predictor supports no splicing effect and the functional RNA data (PMID 24204729) confirms this, the VCEP rule strictly requires ≥3 predictors. Without additional predictors (MaxEntScan, SSF, GeneSplicer, HSF, TraP, varSEAK), BP4 cannot be applied. Details ▾Hide ▴
Evidence considered
- SpliceAI max delta = 0.02 (no predicted splice impact)
- Only 1 of 7 listed splicing predictors available — insufficient for BP4 threshold of ≥3
Still missing
- Need at least 2 more in silico splicing predictors (MaxEntScan
- SSF
- GeneSplicer
- HSF
- TraP
- or varSEAK) to reach the ≥3 threshold
Sources
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.02).
7 paper records listed. 1 cited in the classification.
Cited in the classification
-
PMID 24204729 ↗Identification and characterization of CDH1 germline variants in sporadic gastric cancer patients and in individuals at risk of gastric cancer.Garziera M et al. · 2013Garziera et al. screened CDH1 germline variants in 59 gastric cancer patients, 59 first-degree relatives, 20 autoimmune metaplastic atrophic gastritis patients, and 52 blood donors. The variant c.48+7C>T (designated ID 5) was identified as a novel intronic mutation in one AMAG patient (S121, 51-year-old female with hypergastrinemia) and was absent from all gastric cancer patients and controls. RT-PCR of exons 1-5 from peripheral blood mononuclear cells showed a normal 768 bp transcript identical to wild-type controls on agarose gel. Bidirectional sequencing confirmed no aberrant splicing and no protein truncations or frameshifts. The authors concluded that CDH1 genetic alterations do not appear to play a relevant role in AMAG disease.→ BS3 Names this variant
Source detail
ID 5, a new intronic mutation close to exon 1 (IVS1 c.48+7C>T). ID 5 was found in a female of 51-year-old with hypergastrinemia. We did not find any truncations or frameshifts in the production of the protein associated to this mutation.
Location Table 3 (variant listing); Results para on intronic mutations; Figure 3A (RT-PCR gel); Discussion para on AMAG findings
Context RT-PCR from peripheral blood mononuclear cells (PBMCs); exons 1-5 amplification (~768 bp); agarose gel electrophoresis; bidirectional Sanger sequencing
Other recorded publications
-
PMID 22388873 ↗Familial gastric cancer: guidelines for diagnosis, treatment and periodic surveillance.Kluijt I et al. · 2012Kluijt et al. present clinical practice guidelines from the Dutch Working Group on Hereditary Gastric Cancer covering referral criteria, diagnostic classification, DNA analysis, and surveillance for familial gastric cancer syndromes including HDGC caused by CDH1 mutations. The paper discusses CDH1 germline mutations at the gene level but does not mention NM_004360.5:c.48+7C>T or any specific intronic variant.Does not name this variant
-
PMID 26467025 ↗A Standardized DNA Variant Scoring System for Pathogenicity Assessments in Mendelian Disorders.This paper describes a standardized rules-based DNA variant scoring system for pathogenicity assessment in Mendelian disorders, analyzing over 16,500 pathogenicity assessments on 11,894 variants from 338 genes. The paper discusses general ACMG/AMP classification methodology without mentioning NM_004360.5:c.48+7C>T or CDH1 intronic variants specifically.Does not name this variant
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PMID 25394175 ↗A practice guideline from the American College of Medical Genetics and Genomics and the National Society of Genetic Counselors: referral indications for cancer predisposition assessment.Hampel H et al. · 2015Hampel et al. present ACMG/NSGC practice guidelines for referral indications for cancer predisposition assessment. The paper provides criteria for genetic consultation referral across multiple hereditary cancer syndromes. It does not mention NM_004360.5:c.48+7C>T or discuss specific CDH1 variants.Does not name this variant
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PMID 26324357 ↗American Society of Clinical Oncology Policy Statement Update: Genetic and Genomic Testing for Cancer Susceptibility.Robson ME et al. · 2015Robson et al. present the ASCO policy statement update on genetic and genomic testing for cancer susceptibility, addressing NGS-based multigene panel testing, quality assurance, and access to cancer genetic services. The paper does not mention NM_004360.5:c.48+7C>T or CDH1-specific variants.Does not name this variant
-
PMID 26389210 ↗Genetics of Breast and Gynecologic Cancers (PDQ®): Health Professional Version.PDQ Cancer Genetics Editorial Board · 2002No paper-specific finding is recorded.
-
PMID 26389258 ↗Cancer Genetics Risk Assessment and Counseling (PDQ®): Health Professional Version.PDQ Cancer Genetics Editorial Board · 2002No paper-specific finding is recorded.
Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.
gnomAD v4.1
11 / 1,536,836 recorded alleles
Open source ↗
gnomAD v2.1
Captured gnomAD v2.1 source record
Open source ↗
SpliceAI Lookup
Recorded maximum delta 0.020
Open source ↗
ClinVar
4 Likely benign
Open source ↗
COSMIC
Captured COSMIC 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/142318/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/16-68771373-C-T?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr16-68737470-C-T?dataset=gn…
- gnomAD-Canada ↗http://192.168.4.76:8001/variant/16-68737470-C-T
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_004360.5%3Ac.48%2…
- OncoKB ↗www.oncokb.org/gene/CDH1/?
- COSMIC ↗cancer.sanger.ac.uk/cosmic/mutation/overview?id=121139033
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= 7.15756e-06; MAF= 0.00072%, 11/1536836 alleles, homozygotes = 0) and has highest observed frequency in the Remaining individuals population (AF= 3.33879e-05; MAF= 0.00334%, 2/59902 alleles, homozygotes = 0); grpmax FAF= 3.69e-06.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 1.52693e-05; MAF= 0.00153%, 2/130982 alleles, homozygotes = 0) and has highest observed frequency in the Remaining individuals population (AF= 0.000250125; MAF= 0.02501%, 1/3998 alleles, homozygotes = 0).
gnomAD-Canada
Not available in gnomAD-Canada v1.0.
ClinVar
This variant has been reported in ClinVar as Likely benign (4 clinical laboratories). (ClinVarID = 142318)
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.02).
Somatic
This variant has previously been reported in somatic cancers (COSMIC; COSV105066453, n = 1 times).