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

UUID: 302f2528-fb93-4046-8918-31d40168855a

Approved on: 2023-08-03

Published on: 2023-08-03

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: BS2

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

Expert Panel

CDH1 VCEP

Criteria Specification Information

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

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

• 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
• 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
• 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
• 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.
• 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.
• BA1: Max subpopulation frequency 0.04797% in gnomAD v2.1.1