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]
  • See Evidence submitted by expert panel for details.

Variant: NM_004360.4(CDH1):c.670C>T (p.Arg224Cys)

CA288074

127932 (ClinVar)

Gene: CDH1
Condition: hereditary diffuse gastric cancer
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: d4d12c86-59cb-40a8-92ec-13925d97080a
Approved on: 2019-09-11
Published on: 2019-09-11

HGVS expressions

NM_004360.4:c.670C>T
NM_004360.4(CDH1):c.670C>T (p.Arg224Cys)
NC_000016.10:g.68808831C>T
CM000678.2:g.68808831C>T
NC_000016.9:g.68842734C>T
CM000678.1:g.68842734C>T
NC_000016.8:g.67400235C>T
NG_008021.1:g.76540C>T
ENST00000261769.10:c.670C>T
ENST00000261769.9:c.670C>T
ENST00000422392.6:c.670C>T
ENST00000561751.1:c.437C>T
ENST00000562836.5:n.741C>T
ENST00000564676.5:n.952C>T
ENST00000566510.5:c.531+264C>T
ENST00000566612.5:c.670C>T
ENST00000567320.1:n.180C>T
ENST00000611625.4:c.670C>T
ENST00000612417.4:c.670C>T
ENST00000621016.4:c.670C>T
NM_004360.3:c.670C>T
NM_001317184.1:c.670C>T
NM_001317185.1:c.-946C>T
NM_001317186.1:c.-1150C>T
NM_004360.5:c.670C>T
NM_001317184.2:c.670C>T
NM_001317185.2:c.-946C>T
NM_001317186.2:c.-1150C>T
More

Likely Benign

Met criteria codes 1
BS2
Not Met criteria codes 25
PP1 PP2 PP3 PP4 PM1 PM3 PM5 PM4 PM6 PM2 PVS1 BA1 BS1 BS4 BS3 BP5 BP7 BP4 BP3 BP1 BP2 PS1 PS2 PS3 PS4

Evidence Links 1

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
CDH1 VCEP
The c.670C>T (p.Arg224Cys) variant has been observed in >10 individuals without a diagnosis of diffuse gastric cancer, signet ring tumor or lobular breast cancer and whose family histories do not suggest HDGC (BS2; internal laboratory contributors). In summary, the clinical significance of this variant is classified as likely benign based on BS2 alone. ACMG/AMP criteria applied, as specified by the CDH1 Variant Curation Expert Panel (Variant Interpretation Guidelines Version 2): BS2.
Met criteria codes
BS2
Observed in 392 individuals w/o dx of HDGC
Not Met criteria codes
PP1
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
PP3
Multiple computational tools predict no or low impact.
PP4
One proband with DGC reported in literature.
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
PM5
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
PM6
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM2
Allele frequency of 1.7e-4 in ExAC and gnomAD.
PVS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BA1
Allele frequency of 1.7e-4 in ExAC and gnomAD.
BS1
Allele frequency of 1.7e-4 in ExAC and gnomAD.
BS4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS3
Two functional studies suggest little or no impact on cell adhesion.
Found variant weakly activates E-cadherin induced cell adhesion. PubMed:27582386
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
BP4
Multiple computational tools predict no or low impact.
BP3
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
PS2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS3
Two functional studies suggest little or no impact on cell adhesion.
Found variant weakly activates E-cadherin induced cell adhesion. PubMed:27582386
PS4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Curation History
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