Variant: NM_004360.4(CDH1):c.88C>A (p.Pro30Thr)

CA151524

127933 (ClinVar)

Gene: CDH1

Condition: hereditary diffuse gastric cancer

Inheritance Mode: Autosomal dominant inheritance

UUID: d1e6757d-87b2-428c-a699-e2ac2893485c

Approved on: 2018-11-21

Published on: 2020-06-03

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

Benign

• Met criteria codes: BA1 BS2

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

Expert Panel

CDH1 VCEP

Criteria Specification Information

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: BA1, BS2.

Met criteria codes

• BA1: 0.25% frequency with 178 alleles in European subpopulation meets stand alone criteria for CDH1.
• 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.

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: In silico predictors are only valid for splicing according to CDH1 criteria.
• PP4: 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
• 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: 0.25% frequency with 178 alleles in European subpopulation meets stand alone criteria for CDH1.
• PVS1: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• BS1: 0.25% frequency with 178 alleles in European subpopulation meets stand alone criteria for CDH1.
• 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.
• 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: In silico predictors are only valid for splicing according to CDH1 criteria.
• 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: 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.
• PS4: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline