Variant: NM_004360.4(CDH1):c.308G>A (p.Trp103Ter)

CA396457352

483227 (ClinVar)

Gene: CDH1

Condition: CDH1-related diffuse gastric and lobular breast cancer

Inheritance Mode: Autosomal dominant inheritance

UUID: 2ca4f6ef-375f-4771-ace3-53cb405bc69b

Approved on: 2023-08-29

Published on: 2023-08-29

HGVS expressions

NM_004360.4:c.308G>A
NM_004360.4(CDH1):c.308G>A (p.Trp103Ter)
NC_000016.10:g.68801814G>A
CM000678.2:g.68801814G>A
NC_000016.9:g.68835717G>A
CM000678.1:g.68835717G>A
NC_000016.8:g.67393218G>A
NG_008021.1:g.69523G>A
ENST00000261769.10:c.308G>A
ENST00000261769.9:c.308G>A
ENST00000422392.6:c.308G>A
ENST00000561751.1:n.75G>A
ENST00000562836.5:n.379G>A
ENST00000564676.5:n.590G>A
ENST00000564745.1:n.303G>A
ENST00000566510.5:c.308G>A
ENST00000566612.5:c.308G>A
ENST00000611625.4:c.308G>A
ENST00000612417.4:c.308G>A
ENST00000621016.4:c.308G>A
NM_004360.3:c.308G>A
NM_001317184.1:c.308G>A
NM_001317185.1:c.-1308G>A
NM_001317186.1:c.-1512G>A
NM_004360.5:c.308G>A
NM_001317184.2:c.308G>A
NM_001317185.2:c.-1308G>A
NM_001317186.2:c.-1512G>A
NM_004360.5(CDH1):c.308G>A (p.Trp103Ter)

Pathogenic

• Met criteria codes: PM5_Supporting PVS1 PM2_Supporting PS4_Supporting

• Not Met criteria codes: BP7 BP5 BP3 BP4 BP1 BP2 PS1 PS3 PS2 PM1 PM4 PM3 PM6 PP3 PP2 PP4 PP1 BA1 BS2 BS3 BS4 BS1

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.308G>A p.(Trp103*) variant is predicted to result in a premature stop codon that leads to a truncated or absent protein (PVS1, PM5_Supporting). The variant is absent in the gnomAD cohort (PM2_Supporting; http://gnomad.broadinstitute.org). This variant has been reported in at least one family meeting HDGC clinical criteria (PS4_Supporting; SCV000669020.2). Therefore, this variant meets criteria to be classified as pathogenic based on the ACMG/AMP criteria applied as specified by the CDH1 Variant Curation Expert Panel (Variant Interpretation Guidelines Version 3.1): PVS1, PM2_Supporting, PS4_Supporting, PM5_Supporting.

Met criteria codes

• PM5_Supporting: Apply PM5_Supporting to nonsense/frameshift variants that are predicted/proved to undergo NMD.
• PVS1: Predicted NMD.
• PM2_Supporting: Absent in population databases.
• PS4_Supporting: SCV000669020.2 - diagnosed with diffuse gastric cancer younger than 40.

Not Met criteria codes

• BP7: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• BP5: 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: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• BP1: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• BP2: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PS1: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PS3: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PS2: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PM1: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PM4: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PM3: 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
• PP3: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PP2: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PP4: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PP1: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• BA1: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• BS2: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• BS3: 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
• BS1: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline