Variant: NM_004360.5(CDH1):c.1921C>T (p.Gln641Ter)

CA169506

142826 (ClinVar)

Gene: CDH1

Condition: hereditary diffuse gastric cancer

Inheritance Mode: Autosomal dominant inheritance

UUID: a13097ce-e827-4856-9d7e-7df256027eb9

Approved on: 2020-02-18

Published on: 2020-06-03

HGVS expressions

NM_004360.5:c.1921C>T
NM_004360.5(CDH1):c.1921C>T (p.Gln641Ter)
NC_000016.10:g.68822210C>T
CM000678.2:g.68822210C>T
NC_000016.9:g.68856113C>T
CM000678.1:g.68856113C>T
NC_000016.8:g.67413614C>T
NG_008021.1:g.89919C>T
ENST00000261769.10:c.1921C>T
ENST00000261769.9:c.1921C>T
ENST00000422392.6:c.1738C>T
ENST00000562836.5:n.1992C>T
ENST00000566510.5:c.*587C>T
ENST00000566612.5:c.*161C>T
ENST00000611625.4:c.1984C>T
ENST00000612417.4:c.1830+91C>T
ENST00000621016.4:c.1865+56C>T
NM_004360.3:c.1921C>T
NM_001317184.1:c.1738C>T
NM_001317185.1:c.373C>T
NM_001317186.1:c.-45C>T
NM_004360.4:c.1921C>T
NM_001317184.2:c.1738C>T
NM_001317185.2:c.373C>T
NM_001317186.2:c.-45C>T

Pathogenic

• Met criteria codes: PS4_Supporting PM2 PVS1

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

Expert Panel

Criteria Specification Information

Evidence submitted by expert panel

CDH1 VCEP

The c.1921C>T p.(Gln641Ter) variant is predicted to result in a premature stop codon that leads to a truncated or absent protein (PVS1). The variant is present in <1/100,000 alleles in the gnomAD cohort (PM2; http://gnomad.broadinstitute.org). This variant has been reported in at least one family meeting HDGC clinical criteria (PS4_supporting; SCV000187340.5). 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: PVS1, PM2, PS4_supporting.

Met criteria codes

• PS4_Supporting: SCV000187340.5 - meet HDGC phenotype criteria (same proband as DOI: 10.1200/PO.16.00021)
• PM2: Present in 1 of 251462 alleles (0.001%).
• PVS1: predicted NMD, exon 12 of 16.

Not Met criteria codes

• 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
• 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
• 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
• PM6: 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
• BS2: 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
• 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
• 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