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
  • No ClinVar Id was directly found from the curated document
  • ClinVar Id was derived from the Allele Registry.

Variant: NM_004360.3:c.760G>C

CA396458612

599656 (ClinVar)

Gene: CDH1
Condition: CDH1-related diffuse gastric and lobular breast cancer
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 07c40511-607b-44ff-8565-e682c5ce756f

HGVS expressions

NM_004360.3:c.760G>C
NC_000016.10:g.68810269G>C
CM000678.2:g.68810269G>C
NC_000016.9:g.68844172G>C
CM000678.1:g.68844172G>C
NC_000016.8:g.67401673G>C
NG_008021.1:g.77978G>C
ENST00000261769.10:c.760G>C
ENST00000261769.9:c.760G>C
ENST00000422392.6:c.760G>C
ENST00000561751.1:n.455-1415G>C
ENST00000562836.5:n.831G>C
ENST00000566510.5:c.604G>C
ENST00000566612.5:c.760G>C
ENST00000611625.4:c.760G>C
ENST00000612417.4:c.760G>C
ENST00000621016.4:c.760G>C
NM_001317184.1:c.760G>C
NM_001317185.1:c.-856G>C
NM_001317186.1:c.-1060G>C
NM_004360.4:c.760G>C
NM_004360.5:c.760G>C
NM_001317184.2:c.760G>C
NM_001317185.2:c.-856G>C
NM_001317186.2:c.-1060G>C
NM_004360.5(CDH1):c.760G>C (p.Asp254His)

Uncertain Significance

Met criteria codes 2
PS4_Supporting PM2_Supporting
Not Met criteria codes 24
PS2 PS1 PS3 BA1 PP4 PP1 PP2 PP3 PM1 PM4 PM5 PM3 PM6 PVS1 BS2 BS4 BS3 BS1 BP3 BP2 BP1 BP4 BP5 BP7

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.760G>C (p.Asp254His) variant is absent in the gnomAD cohort (PM2_Supporting). This variant has been reported in at least one family meeting HDGC clinical criteria (PS4_Supporting; internal laboratory contributor). 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, PS4_Supporting.
Met criteria codes
PS4_Supporting
1 proband diagnosed with DGC at 58, father also diagnosed with unspecified gastric cancer.
PM2_Supporting
Absent from population databases.
Not Met criteria codes
PS2
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
Clinical validity unclear so did not give this PS3.
BA1
Absent from population databases.
PP4
Proband diagnosed with DGC at 58, father also diagnosed with unspecified gastric cancer.
PP1
insufficient co-segregation to meet criteria.
PP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP3
Exceeds impact threshold in REVEL.
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
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
PVS1
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
BS4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS3
Clinical validity unclear so did not give this PS3.
BS1
Absent from population databases.
BP3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP2
Father is PMS2+, taking this to mean IHC positive.
BP1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP4
Exceeds impact threshold in REVEL.
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
Approved on: 2023-08-21
Published on: 2023-08-21
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