Variant: NM_004360.5(CDH1):c.1354_1357del (p.Leu452fs)

CA10588623

265543 (ClinVar)

Gene: CDH1

Condition: CDH1-related diffuse gastric and lobular breast cancer

Inheritance Mode: Autosomal dominant inheritance

UUID: 9d69b4f3-8f18-42f4-9ad0-719f091202ce

Approved on: 2023-08-04

Published on: 2023-08-04

HGVS expressions

NM_004360.5:c.1354_1357del
NM_004360.5(CDH1):c.1354_1357del (p.Leu452fs)
NC_000016.10:g.68815548_68815551del
CM000678.2:g.68815548_68815551del
NC_000016.9:g.68849451_68849454del
CM000678.1:g.68849451_68849454del
NC_000016.8:g.67406952_67406955del
NG_008021.1:g.83257_83260del
ENST00000261769.10:c.1354_1357del
ENST00000261769.9:c.1354_1357del
ENST00000422392.6:c.1171_1174del
ENST00000562836.5:n.1425_1428del
ENST00000566510.5:c.*20_*23del
ENST00000566612.5:c.1354_1357del
ENST00000611625.4:c.1417_1420del
ENST00000612417.4:c.1354_1357del
ENST00000621016.4:c.1354_1357del
NM_004360.3:c.1354_1357del
NM_001317184.1:c.1171_1174del
NM_001317185.1:c.-195_-192del
NM_001317186.1:c.-466_-463del
NM_004360.4:c.1354_1357del
NM_001317184.2:c.1171_1174del
NM_001317185.2:c.-195_-192del
NM_001317186.2:c.-466_-463del

Pathogenic

• Met criteria codes: PM2_Supporting PM5_Supporting PVS1

• Not Met criteria codes: PM6 PM4 PM1 PM3 BS2 BS3 BS4 BS1 BP7 BP5 BP3 BP4 BP1 BP2 PS1 PS3 PS2 PS4 PP3 PP2 PP4 PP1 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.1354_1357delCTAC p.(Leu452fs) 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

• PM2_Supporting: Absent in population databases.
• PM5_Supporting: Exon 10 of 16, predicted NMD.
• PVS1: Exon 10 of 16, predicted NMD.

Not Met criteria codes

• PM6: 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
• PM1: 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
• 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
• 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
• PS4: SCV000322523.8 - Proband 1 Unaffected in 30s (does not meet HDGC criteria); proband 2 Hodgkin's lymphoma (FHx gastric but pathology not confirmed).
• 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