Variant: NM_004360.4(CDH1):c.225C>G (p.Phe75Leu)

CA8129814

406646 (ClinVar)

Gene: CDH1

Condition: CDH1-related diffuse gastric and lobular breast cancer

Inheritance Mode: Autosomal dominant inheritance

UUID: 93ac705b-e85f-467d-b189-38bc00c12f90

Approved on: 2023-08-21

Published on: 2023-08-21

HGVS expressions

NM_004360.4:c.225C>G
NM_004360.4(CDH1):c.225C>G (p.Phe75Leu)
NC_000016.10:g.68801731C>G
CM000678.2:g.68801731C>G
NC_000016.9:g.68835634C>G
CM000678.1:g.68835634C>G
NC_000016.8:g.67393135C>G
NG_008021.1:g.69440C>G
ENST00000261769.10:c.225C>G
ENST00000261769.9:c.225C>G
ENST00000422392.6:c.225C>G
ENST00000562836.5:n.296C>G
ENST00000564676.5:n.507C>G
ENST00000564745.1:n.220C>G
ENST00000566510.5:c.225C>G
ENST00000566612.5:c.225C>G
ENST00000611625.4:c.225C>G
ENST00000612417.4:c.225C>G
ENST00000621016.4:c.225C>G
NM_004360.3:c.225C>G
NM_001317184.1:c.225C>G
NM_001317185.1:c.-1391C>G
NM_001317186.1:c.-1595C>G
NM_004360.5:c.225C>G
NM_001317184.2:c.225C>G
NM_001317185.2:c.-1391C>G
NM_001317186.2:c.-1595C>G
NM_004360.5(CDH1):c.225C>G (p.Phe75Leu)

Uncertain Significance

• Met criteria codes: PM2_Supporting

• Not Met criteria codes: PM6 PM5 PM4 PM1 PM3 PVS1 BS2 BS3 BS4 BS1 BP7 BP5 BP3 BP4 BP1 BP2 PS1 PS3 PS2 PS4 PP3 PP2 PP4 PP1 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.225C>G p.(Phe75Leu)variant is present in <1/100,000 alleles in the gnomAD cohort (PM2_Supporting; http://gnomad.broadinstitute.org). No additional evidence met criteria for consideration. In summary, the clinical significance of this variant is uncertain. ACMG/AMP criteria applied, as specified by the CDH1 Variant Curation Expert Panel (Variant Interpretation Guidelines Version 3.1): PM2_Supporting.

Met criteria codes

• PM2_Supporting: Observed in 1 of 246,180 alleles (0.000398%) in gnomAD v2.0.2 (<1 in 100,000 alleles, <0.001%). gnomAD v2.1.1 - seen in 1 of 251,414 alleles (0.000398%).

Not Met criteria codes

• PM6: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PM5: c.223T>C (p.Phe75Leu) - in ClinVar as Likely benign(1);Uncertain significance(1). c.224T>G (p.Phe75Cys) - in ClinVar as Uncertain significance(1). c.225C>A (p.Phe75Leu) - in ClinVar as Uncertain significance(1).
• PM4: 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
• PVS1: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• BS2: Invitae (SCV000545429.2) - one proband cancer-free, FHx does not meet HDGC criteria (ClinGen guidelines require at least 3 individuals).
• BS3: 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
• BS1: 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
• BP5: 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
• BP2: 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
• PS3: 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: Not reported in published studies. Invitae (SCV000545429.2) - proband cancer-free, FHx does not meet HDGC criteria.
• 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
• 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
• BA1: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline