Evidence Repository
The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
Link to SEPIO compliant JSON-LD document

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
Link to MONDO
UUID: 93ac705b-e85f-467d-b189-38bc00c12f90

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 1
PM2_Supporting
Not Met criteria codes 25
PS1 PS3 PS2 PS4 PVS1 PP3 PP2 PP4 PP1 BA1 PM5 PM4 PM1 PM3 PM6 BS2 BS3 BS4 BS1 BP3 BP4 BP1 BP2 BP7 BP5

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specification: ClinGen CDH1 Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines Version 3.1

Criteria Specification Approval History
Criteria Specifications for this VCEP
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
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.
PVS1
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
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
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
PM6
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
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
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
Approved on: 2023-08-21
Published on: 2023-08-21
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