Variant: NM_004360.5(CDH1):c.125C>T (p.Pro42Leu)

CA10580073

231745 (ClinVar)

Gene: CDH1

Condition: CDH1-related diffuse gastric and lobular breast cancer

Inheritance Mode: Autosomal dominant inheritance

UUID: 769d2160-06b8-4eb7-894a-450600260917

Approved on: 2023-08-02

Published on: 2023-08-02

HGVS expressions

NM_004360.5:c.125C>T
NM_004360.5(CDH1):c.125C>T (p.Pro42Leu)
NC_000016.10:g.68738373C>T
CM000678.2:g.68738373C>T
NC_000016.9:g.68772276C>T
CM000678.1:g.68772276C>T
NC_000016.8:g.67329777C>T
NG_008021.1:g.6082C>T
ENST00000261769.10:c.125C>T
ENST00000261769.9:c.125C>T
ENST00000422392.6:c.125C>T
ENST00000566510.5:c.125C>T
ENST00000566612.5:c.125C>T
ENST00000611625.4:c.125C>T
ENST00000612417.4:c.125C>T
ENST00000621016.4:c.125C>T
NM_004360.3:c.125C>T
NM_001317184.1:c.125C>T
NM_001317185.1:c.-1491C>T
NM_001317186.1:c.-1695C>T
NM_004360.4:c.125C>T
NM_001317184.2:c.125C>T
NM_001317185.2:c.-1491C>T
NM_001317186.2:c.-1695C>T

Likely Benign

• Met criteria codes: BS2

• Not Met criteria codes: BA1 BP5 BP7 BP2 BP3 BP4 BP1 BS4 BS3 BS1 PVS1 PP4 PP1 PP3 PP2 PM6 PM2 PS2 PS4 PS3 PS1 PM3 PM1 PM4 PM5

Expert Panel

CDH1 VCEP

Criteria Specification Information

Evidence submitted by expert panel

CDH1 VCEP

The c.125C>T (NM_004360.5) variant in CDH1 is a missense variant predicted to cause substitution of Pro by Leu at amino acid 42 (p.Pro42Leu). This variant has been observed in more than 10 heterozygous individuals with no DGC, SRC tumours and whose families do not suggest HDGC (BS2; GeneDx, Invitae, Color). In summary, the CDH1 VCEP classified the variant as likely benign for DGLBCS based on BS2 alone based on the ACMG/AMP criteria applied, as specified by the ClinGen CDH1 VCEP: BS2. (CDH1 VCEP specifications version 3.1; 04/24/2023)

Met criteria codes

• BS2: This variant has been observed in more than 10 heterozygous individuals with no DGC, SRC tumours and whose families do not suggest HDGC (BS2; GeneDx, Invitae, Color).

Not Met criteria codes

• BA1: Variant absent in gnomAD v2.1.1. Variant present in 2 of 143312 alleles in gnomAD v3 (2 of 13658 alleles in Latino population)
• 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
• 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 in gnomAD v2.1.1. Variant present in 2 of 143312 alleles in gnomAD v3 (2 of 13658 alleles in Latino population)
• PVS1: 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
• PM6: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PM2: Variant absent in gnomAD v2.1.1. Variant present in 2 of 143312 alleles in gnomAD v3 (2 of 13658 alleles in Latino population)
• PS2: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PS4: 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
• 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
• PM5: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline