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LYFE SCIENCES
Project: HERA
NM_004360.5:c.1888C>G
p.Leu630Val  ·  CDH1
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Classification rationale
1

The CDH1 NM_004360.5:c.1888C>G (p.Leu630Val) variant has been reported in ClinVar with an expert-panel benign classification, alongside multiple benign and likely benign clinical laboratory submissions.

clinvar ↗
2

This variant is present in population databases at a frequency above the CDH1 benign stand-alone threshold, with the highest observed East Asian frequency of 0.48622% in gnomAD v2.1 and 0.56147% in gnomAD v4.1.

gnomad_v2 ↗ gnomad_v4 ↗ gnomad_canada ↗ cspec ↗
3

SpliceAI predicts no significant splice impact for this variant with a maximum delta score of 0.02; REVEL 0.345 and BayesDel -0.164621 are available as supporting context but are not used to apply CDH1 missense PP3 or BP4.

spliceai ↗ cspec ↗
Applied criteria
Met
Not met
Not assessed
N/A
Very strong
Strong
Moderate
Supporting
Pathogenic evidence
PVS
PVS1
PS
PS1
PS2
PS3
PS4
PM
PM1
PM2
PM3
PM4
PM5
PM6
PP
PP1
PP2
PP3
PP4
PP5
Benign evidence
BA
BA1
BS
BS1
BS2
BS3
BS4
BP
BP1
BP2
BP3
BP4
BP5
BP6
BP7
PVS1
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Rationale
Select a criterion to inspect its explanation.
Evidence used
  • —
Gaps remaining
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Rule
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Publications
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Research and evidence
gnomAD v2.1 evidence
v2.1
gnomAD v4.1 evidence
v4.1
01
Population
gnomAD v2.1This variant is present in gnomAD v2.1 (AF= 0.000357057; MAF= 0.03571%, 101/282868 alleles, homozygotes = 0) and has highest observed frequency in the East Asian population (AF= 0.00486216; MAF= 0.48622%, 97/19950 alleles, homozygotes = 0); grpmax FAF= 0.00412524.
gnomAD v4.1This variant is present in gnomAD v4.1 (AF= 0.000165413; MAF= 0.01654%, 267/1614146 alleles, homozygotes = 0) and has highest observed frequency in the East Asian population (AF= 0.00561472; MAF= 0.56147%, 252/44882 alleles, homozygotes = 0); grpmax FAF= 0.00504519.
gnomAD CanadaThis variant is present in gnomAD-Canada v1.0 (AF= 0.000325768; MAF= 0.03258%, 6/18418 alleles, homozygotes = 0) and has highest observed frequency in the eas population (AF= 0.00224215; grpmax FAF95= 0.00061019).
gnomAD v2 ↗ gnomAD v4 ↗ gnomAD 🇨🇦 ↗
ClinVar evidence
02
ClinVar
This variant has been reported in ClinVar as Benign (7 clinical laboratories) and as Likely benign (5 clinical laboratories) and as Benign by Clingen Gastric Cancer Variant Curation Expert Panel (expert panel). (ClinVarID = 133846)
ClinVar ↗
Functional evidence
03
Functional
OncoKB: Unknown Oncogenic Effect
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
OncoKB ↗
In silico evidence
04
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.02). REVEL score = 0.345. BayesDel score = -0.164621.
SpliceAI ↗
COSMIC evidence
05
COSMIC
This variant does not lie in a statistically significant hotspot. This variant has previously been reported in somatic cancers (COSMIC; COSV55733235, n = 5 times).
COSMIC ↗
Cancer hotspots evidence
06
Cancer hotspots Not found
This variant does not lie in a statistically significant hotspot.
ResidueL630
Hotspots ↗