Variant: NM_004360.5(CDH1):c.11G>A (p.Trp4Ter)

CA396451240

918853 (ClinVar)

Gene: CDH1

Condition: CDH1-related diffuse gastric and lobular breast cancer

Inheritance Mode: Autosomal dominant inheritance

UUID: 779fb7a8-6e03-4a37-bab2-3eee5f80110f

Approved on: 2023-08-04

Published on: 2023-08-04

HGVS expressions

NM_004360.5:c.11G>A
NM_004360.5(CDH1):c.11G>A (p.Trp4Ter)
NC_000016.10:g.68737426G>A
CM000678.2:g.68737426G>A
NC_000016.9:g.68771329G>A
CM000678.1:g.68771329G>A
NC_000016.8:g.67328830G>A
NG_008021.1:g.5135G>A
ENST00000261769.10:c.11G>A
ENST00000261769.9:c.11G>A
ENST00000422392.6:c.11G>A
ENST00000566510.5:c.11G>A
ENST00000566612.5:c.11G>A
ENST00000611625.4:c.11G>A
ENST00000612417.4:c.11G>A
ENST00000621016.4:c.11G>A
NM_004360.3:c.11G>A
NM_001317184.1:c.11G>A
NM_001317185.1:c.-1605G>A
NM_001317186.1:c.-1809G>A
NM_004360.4:c.11G>A
NM_001317184.2:c.11G>A
NM_001317185.2:c.-1605G>A
NM_001317186.2:c.-1809G>A

Pathogenic

• Met criteria codes: PM5_Supporting PM2_Supporting PVS1

• Not Met criteria codes: BS2 BS4 BS3 BS1 BP3 BP4 BP1 BP2 BP7 BP5 PS1 PS4 PS2 PS3 BA1 PP3 PP2 PP1 PP4 PM4 PM3 PM1 PM6

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.11G>A (p.Trp4Ter) variant is predicted to result in a premature stop codon that leads to nonsense mediate decay (PVS1 and PM5_supporting). The variant is absent in the gnomAD cohort (PM2_supporting; http://gnomad.broadinstitute.org). 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 (CDH1 VCEP specifications version 3.1): PVS1, PM2_supporting, PM5_supporting.

Met criteria codes

• PM5_Supporting: Creating a premature translation stop signal in codon 4 in exon 1 is expected to result in nonsense mediate decay.
• PM2_Supporting: absence in controls. not in gnomAD, 1000 genomics and ESP with adequate coverage.
• PVS1: Creating a premature translation stop signal in codon 4 in exon 1 is expected to result in an absent or non-functional protein product

Not Met criteria codes

• BS2: 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: 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
• 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
• 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
• PS1: .
• PS4: 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
• PS3: 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
• 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
• PP1: 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
• 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
• PM1: Located in exon 1, the signal peptide.
• PM6: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline