Evidence Repository
The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
Link to SEPIO compliant JSON-LD document

Variant: NM_004360.5(CDH1):c.214G>A (p.Asp72Asn)

CA294297

136064 (ClinVar)

Gene: CDH1
Condition: CDH1-related diffuse gastric and lobular breast cancer
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 302f2528-fb93-4046-8918-31d40168855a

HGVS expressions

NM_004360.5:c.214G>A
NM_004360.5(CDH1):c.214G>A (p.Asp72Asn)
NC_000016.10:g.68801720G>A
CM000678.2:g.68801720G>A
NC_000016.9:g.68835623G>A
CM000678.1:g.68835623G>A
NC_000016.8:g.67393124G>A
NG_008021.1:g.69429G>A
ENST00000261769.10:c.214G>A
ENST00000261769.9:c.214G>A
ENST00000422392.6:c.214G>A
ENST00000562836.5:n.285G>A
ENST00000564676.5:n.496G>A
ENST00000564745.1:n.209G>A
ENST00000566510.5:c.214G>A
ENST00000566612.5:c.214G>A
ENST00000611625.4:c.214G>A
ENST00000612417.4:c.214G>A
ENST00000621016.4:c.214G>A
NM_004360.3:c.214G>A
NM_001317184.1:c.214G>A
NM_001317185.1:c.-1402G>A
NM_001317186.1:c.-1606G>A
NM_004360.4:c.214G>A
NM_001317184.2:c.214G>A
NM_001317185.2:c.-1402G>A
NM_001317186.2:c.-1606G>A

Likely Benign

Met criteria codes 1
BS2
Not Met criteria codes 25
PS1 PS2 PS4 PS3 BA1 PP4 PP1 PP3 PP2 PM5 PM3 PM1 PM4 PM6 PM2 PVS1 BS4 BS3 BS1 BP2 BP3 BP4 BP1 BP5 BP7

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specification: ClinGen CDH1 Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines Version 3.1

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
CDH1 VCEP
The c.214G>A (p.Asp72Asn) missense variant has a maximum subpopulation frequency of 0.048% in the gnomAD v2.1.1 cohort (http://gnomad.broadinstitute.org). This variant has been observed in over 300 probands not meeting HDGC phenotype criteria (BS2; SCV000210893.13, SCV000186096.8, SCV000166549.12). In summary, this variant meets criteria to be classified as Likely Benign based on the ACMG/AMP criteria applied as specified by the CDH1 Variant Curation Expert Panel: BS2. (CDH1 VCEP specifications version 3.1; 06/26/2023)
Met criteria codes
BS2
>300 probands/families not meeting HDGC criteria
Not Met criteria codes
PS1
Not applicable for CDH1.
PS2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS3
This rule can only be applied to demonstrate splicing defects.
BA1
Max subpopulation frequency 0.04797% in gnomAD v2.1.1
PP4
Not applicable for CDH1.
PP1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP3
Do not use protein-based computational prediction models for missense variants.
PP2
Not applicable for CDH1.
PM5
PM5_supporting is applicable to nonsense and frameshift variants that are predicted/proved to undergo NMD or located upstream of the last known pathogenic truncating variant. Site-specific recommendations for the application of PM5_Supporting for canonical splicing variants.
PM3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM1
Not applicable for CDH1.
PM4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM6
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM2
Max subpopulation frequency 0.04797% in gnomAD v2.1.1
PVS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS3
This rule can only be used to demonstrate lack of splicing and can only be applied to Synonymous, Intronic or Non-coding variants.
BS1
Max subpopulation frequency 0.04797% in gnomAD v2.1.1
BP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP4
Do not use protein-based computational prediction models for missense variants.
BP1
Not applicable for CDH1.
BP5
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP7
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Approved on: 2023-08-03
Published on: 2023-08-03
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