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]
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Variant: NM_004360.5(CDH1):c.512T>G (p.Phe171Cys)

CA8129871

423041 (ClinVar)

Gene: CDH1
Condition: CDH1-related diffuse gastric and lobular breast cancer
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 3a340a0d-25b6-41ce-96e4-0b17f8aad1f6
Approved on: 2023-08-21
Published on: 2023-08-21

HGVS expressions

NM_004360.5:c.512T>G
NM_004360.5(CDH1):c.512T>G (p.Phe171Cys)
NC_000016.10:g.68808548T>G
CM000678.2:g.68808548T>G
NC_000016.9:g.68842451T>G
CM000678.1:g.68842451T>G
NC_000016.8:g.67399952T>G
NG_008021.1:g.76257T>G
ENST00000261769.10:c.512T>G
ENST00000261769.9:c.512T>G
ENST00000422392.6:c.512T>G
ENST00000561751.1:n.279T>G
ENST00000562836.5:n.583T>G
ENST00000564676.5:n.794T>G
ENST00000564745.1:n.507T>G
ENST00000566510.5:c.512T>G
ENST00000566612.5:c.512T>G
ENST00000567320.1:n.22T>G
ENST00000611625.4:c.512T>G
ENST00000612417.4:c.512T>G
ENST00000621016.4:c.512T>G
NM_004360.3:c.512T>G
NM_001317184.1:c.512T>G
NM_001317185.1:c.-1104T>G
NM_001317186.1:c.-1308T>G
NM_004360.4:c.512T>G
NM_001317184.2:c.512T>G
NM_001317185.2:c.-1104T>G
NM_001317186.2:c.-1308T>G

Uncertain Significance

Met criteria codes 2
PM2_Supporting BS2_Supporting
Not Met criteria codes 24
PVS1 BS4 BS3 BS1 BP4 BP1 BP3 BP2 BP7 BP5 PS1 PS2 PS4 PS3 BA1 PP3 PP2 PP4 PP1 PM6 PM4 PM5 PM3 PM1

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.512T>G (p.Phe171Cys) variant has an allele frequency: 1:251320 (<one out 100.000 alleles) in the gnomAD cohort (PM2_Supporting; http://https://gnomad.broadinstitute.org/). It has been observed in 4 probands w/o DGS, SRC tumor or LBC and whose families do not suggest HDGC (BS2_Supporting; SCV000572669.4, SCV000637836.3). In summary, this variant meets criteria to be classified as VUS based on the ACMG/AMP criteria applied as specified by the CDH1 Variant Curation Expert Panel (Variant Interpretation Guidelines Version 3.1): PM2_Supporting, BS2_Supporting.
Met criteria codes
PM2_Supporting
allele frequency: 1:251320 (<one out 100.000 alleles in gnomAD)
BS2_Supporting
Observed in 4 probands w/o DGS, SRC tumor or LBC and whose families do not suggest HDGC. SCV000637836.3: Proband #1: unaffected male at 40s. Proband #2: female with diffuse gastric cancer at 60s. Proband #3: female with breast cancer (IDC, ER-PR-HER2+) at 50s. Proband #4: female with metastatic diffuse gastric cancer at 40s. Proband #5: female with breast cancer (IDC) at 50s (carries RAD50 pathogenic variant). SCV000572669.4: Proband#1: unaffected male in his 60s
Not Met criteria codes
PVS1
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
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
BP3
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
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
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
BA1
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
PM6
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
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
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