Variant: NM_004360.4(CDH1):c.1711+2_1711+7delTAAGGG

CA195350

186618 (ClinVar)

Gene: CDH1

Condition: CDH1-related diffuse gastric and lobular breast cancer

Inheritance Mode: Autosomal dominant inheritance

UUID: b1199911-3a8f-4212-a682-fae7a79aae9b

Approved on: 2023-08-24

Published on: 2023-08-24

HGVS expressions

NM_004360.4:c.1711+2_1711+7del
NM_004360.4(CDH1):c.1711+2_1711+7delTAAGGG
NC_000016.10:g.68819427_68819432del
CM000678.2:g.68819427_68819432del
NC_000016.9:g.68853330_68853335del
CM000678.1:g.68853330_68853335del
NC_000016.8:g.67410831_67410836del
NG_008021.1:g.87136_87141del
ENST00000261769.10:c.1711+2_1711+7del
ENST00000261769.9:c.1711+2_1711+7del
ENST00000422392.6:c.1528+2_1528+7del
ENST00000562836.5:n.1782+2_1782+7del
ENST00000566510.5:c.*377+2_*377+7del
ENST00000566612.5:c.1566-2574_1566-2569del
ENST00000611625.4:c.1774+2_1774+7del
ENST00000612417.4:c.1711+2_1711+7del
ENST00000621016.4:c.1711+2_1711+7del
NM_004360.3:c.1711+2_1711+7del
NM_001317184.1:c.1528+2_1528+7del
NM_001317185.1:c.163+2_163+7del
NM_001317186.1:c.-254-2574_-254-2569del
NM_004360.5:c.1711+2_1711+7del
NM_001317184.2:c.1528+2_1528+7del
NM_001317185.2:c.163+2_163+7del
NM_001317186.2:c.-254-2574_-254-2569del
NM_004360.5(CDH1):c.1711+2_1711+7del

Likely Pathogenic

• Met criteria codes: PM5_Supporting PVS1_Strong PM2_Supporting PS4_Supporting

• Not Met criteria codes: BS2 BS4 BS3 BS1 BP2 BP3 BP4 BP1 BP5 BP7 PS2 PS3 PS1 BA1 PP1 PP4 PP3 PP2 PM3 PM1 PM4 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.1711+2_1711+7delTAAGGG variant is a canonical splice variant predicted to result in a truncated or absent protein (PVS1_Strong, PM5_Supporting). This variant is absent in the gnomAD cohort (PM2_Supporting; http://gnomad.broadinstitute.org). The variant has been reported in at least one family meeting HDGC clinical criteria (PS4_Supporting; SCV000217020.4). In summary, 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_Strong, PM2_Supporting, PS4_Supporting, PM5_Supporting.

Met criteria codes

• PM5_Supporting: Apply PM5_Supporting to the variant with the alteration at canonical splicing site.
• PVS1_Strong: A 6 bp deletion including +2 of the canonical donor splice site in intron 11, which is predicted to result in a truncated or loss of the protein
• PM2_Supporting: Absent in gnomAD
• PS4_Supporting: One family meets HDGC clinical criteria (SCV000217020.4).

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
• 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
• 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
• 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
• PS1: 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
• 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
• 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
• 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
• PM6: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline