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.88C>A (p.Pro30Thr)

CA151524

127933 (ClinVar)

Gene: CDH1
Condition: CDH1-related diffuse gastric and lobular breast cancer
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: d1e6757d-87b2-428c-a699-e2ac2893485c

HGVS expressions

NM_004360.4:c.88C>A
NM_004360.4(CDH1):c.88C>A (p.Pro30Thr)
NC_000016.10:g.68738336C>A
CM000678.2:g.68738336C>A
NC_000016.9:g.68772239C>A
CM000678.1:g.68772239C>A
NC_000016.8:g.67329740C>A
NG_008021.1:g.6045C>A
ENST00000261769.10:c.88C>A
ENST00000261769.9:c.88C>A
ENST00000422392.6:c.88C>A
ENST00000566510.5:c.88C>A
ENST00000566612.5:c.88C>A
ENST00000611625.4:c.88C>A
ENST00000612417.4:c.88C>A
ENST00000621016.4:c.88C>A
NM_004360.3:c.88C>A
NM_001317184.1:c.88C>A
NM_001317185.1:c.-1528C>A
NM_001317186.1:c.-1732C>A
NM_004360.5:c.88C>A
NM_001317184.2:c.88C>A
NM_001317185.2:c.-1528C>A
NM_001317186.2:c.-1732C>A
NM_004360.5(CDH1):c.88C>A (p.Pro30Thr)

Benign

Met criteria codes 2
BS2 BA1
Not Met criteria codes 24
PVS1 BS4 BS3 BS1 BP5 BP7 BP3 BP2 BP1 BP4 PS2 PS4 PS1 PS3 PP4 PP1 PP2 PP3 PM6 PM2 PM4 PM3 PM1 PM5

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.88C>A (p.Pro30Thr) variant has an allele frequency of 0.00249 (0.25%, 178/71372 alleles) in the European (non-Finnish) subpopulation of the gnomAD cohort (BA1). In addition to meeting stand along criteria for a benign classification, this variant has also been seen in >900 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, this variant meets criteria to be classified as benign. ACMG/AMP criteria applied, as specified by the CDH1 Variant Curation Expert Panel (Variant Interpretation Guidelines Version 3.1): BA1, BS2.
Met criteria codes
BS2
Vast majority of patients with this variant had neither lobular breast cancer nor gastric cancer. 929 non-HDGC individuals with allele number of 178,576.
BA1
0.25% frequency with 178 alleles in European subpopulation meets stand alone criteria for CDH1.
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
Mutation resulted in abnormal localization and reduced aggregation in CHO cells. Invasion and expression not significantly different to wild type (Vogelaar et al.) Does not meet CDH1 criteria.
BS1
0.25% frequency with 178 alleles in European subpopulation meets stand alone criteria for CDH1.
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
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
BP1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP4
In silico predictors are only valid for splicing according to CDH1 criteria.
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
PS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS3
Mutation resulted in abnormal localization and reduced aggregation in CHO cells. Invasion and expression not significantly different to wild type (Vogelaar et al.) Does not meet CDH1 criteria.
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
PP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP3
In silico predictors are only valid for splicing according to CDH1 criteria.
PM6
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM2
0.25% frequency with 178 alleles in European subpopulation meets stand alone criteria for CDH1.
PM4
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
PM5
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Approved on: 2023-08-17
Published on: 2023-08-17
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