Variant: NM_004360.5(CDH1):c.1341del (p.Lys447fs)

CA645509535

439040 (ClinVar)

Gene: CDH1

Condition: CDH1-related diffuse gastric and lobular breast cancer

Inheritance Mode: Autosomal dominant inheritance

UUID: eac3f3c3-6411-4f1e-8bd0-9dd4b76316e8

Approved on: 2023-08-04

Published on: 2023-08-04

HGVS expressions

NM_004360.5:c.1341del
NM_004360.5(CDH1):c.1341del (p.Lys447fs)
NC_000016.10:g.68815535del
CM000678.2:g.68815535del
NC_000016.9:g.68849438del
CM000678.1:g.68849438del
NC_000016.8:g.67406939del
NG_008021.1:g.83244del
ENST00000261769.10:c.1341del
ENST00000261769.9:c.1341del
ENST00000422392.6:c.1158del
ENST00000562836.5:n.1412del
ENST00000566510.5:c.*7del
ENST00000566612.5:c.1341del
ENST00000611625.4:c.1404del
ENST00000612417.4:c.1341del
ENST00000621016.4:c.1341del
NM_004360.3:c.1341del
NM_001317184.1:c.1158del
NM_001317185.1:c.-208del
NM_001317186.1:c.-479del
NM_004360.4:c.1341del
NM_001317184.2:c.1158del
NM_001317185.2:c.-208del
NM_001317186.2:c.-479del

Pathogenic

• Met criteria codes: PM2_Supporting PM5_Supporting PVS1

• Not Met criteria codes: PM6 PM3 PM1 PM4 BS2 BS4 BS3 BS1 BP5 BP7 BP2 BP3 BP4 BP1 PS2 PS4 PS3 PS1 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.1341del (p.Lys447fs) 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: Variant absent from gnomAD
• PM5_Supporting: Variant predicted to cause NMD with premature stop at amino acid 454
• PVS1: Variant predicted to cause NMD with premature stop at amino acid 454

Not Met criteria codes

• PM6: 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: 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
• 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: Variant absent from gnomAD
• 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
• 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: 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
• PS2: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PS4: 1 family with multiple reports of gastric cancer, however pathology not confirmed (internal lab contributor).
• PS3: 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
• 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
• 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
• BA1: Variant absent from gnomAD