Variant: NM_004360.5(CDH1):c.2296-1G>A

CA16042157

371806 (ClinVar)

Gene: CDH1

Condition: hereditary diffuse gastric cancer

Inheritance Mode: Autosomal dominant inheritance

UUID: 62569505-a102-4142-ab42-cedf24c4765b

Approved on: 2021-05-04

Published on: 2021-05-04

HGVS expressions

NM_004360.5:c.2296-1G>A
NM_004360.5(CDH1):c.2296-1G>A
NC_000016.10:g.68829653G>A
CM000678.2:g.68829653G>A
NC_000016.9:g.68863556G>A
CM000678.1:g.68863556G>A
NC_000016.8:g.67421057G>A
NG_008021.1:g.97362G>A
ENST00000261769.10:c.2296-1G>A
ENST00000261769.9:c.2296-1G>A
ENST00000422392.6:c.2113-1G>A
ENST00000562118.1:n.514-1G>A
ENST00000562836.5:n.2367-1G>A
ENST00000566510.5:c.*962-1G>A
ENST00000566612.5:c.*536-1G>A
ENST00000611625.4:c.2359-1G>A
ENST00000612417.4:c.1853+3099G>A
ENST00000621016.4:c.1866-4550G>A
NM_004360.3:c.2296-1G>A
NM_001317184.1:c.2113-1G>A
NM_001317185.1:c.748-1G>A
NM_001317186.1:c.331-1G>A
NM_004360.4:c.2296-1G>A
NM_001317184.2:c.2113-1G>A
NM_001317185.2:c.748-1G>A
NM_001317186.2:c.331-1G>A

Likely Pathogenic

• Met criteria codes: PS4_Moderate PVS1_Strong PM2_Supporting

• Not Met criteria codes: PP1 PP2 PP3 PP4 PM1 PM3 PM5 PM4 PS1 PS2 PS3 PM6 BA1 BP5 BP7 BP4 BP3 BP1 BP2 BS1 BS4 BS3 BS2

Expert Panel

Criteria Specification Information

Evidence submitted by expert panel

CDH1 VCEP

The c.2296-1G>A variant is a canonical splice variant predicted to result in a truncated or absent protein (PVS1_Strong). This variant is absent in the gnomAD cohort (PM2_supporting; http://gnomad.broadinstitute.org). This variant has been reported in at least three familes meeting HDGC clinical criteria (PS4_moderate; SCV000580714.3). In summary, this variant meets criteria to be classified as likely pathogenic based on the ACMG/AMP criteria applied as specified by the CDH1 Variant Curation Expert Panel (Variant Interpretation Guidelines Version 3): PVS1_strong, PS4_moderate, PM2_supporting.

Met criteria codes

• PS4_Moderate: 3 families that meet HDGC criteria (SCV000580714.3). 2 families that have insufficient information to determine if they meet HDCG criteria
• PVS1_Strong: Intron 14 canonical acceptor splice site variant. Predicted loss of native site and creation of de novo acceptor leading to 1 bp deletion. RNA studies not conducted.
• PM2_Supporting: Absent in gnomAD v2.1 and v3.0, in a region of sufficient coverage

Not Met criteria codes

• PP1: <3 (2) affected meioses in one family
• PP2: 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
• PP4: 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
• PM5: 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
• PS1: 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
• PM6: 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
• 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
• BP4: 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
• 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
• BS1: 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
• BS2: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline