Variant: NM_004360.4(CDH1):c.892G>A (p.Ala298Thr)

CA211397

41787 (ClinVar)

Gene: CDH1

Condition: CDH1-related diffuse gastric and lobular breast cancer

Inheritance Mode: Autosomal dominant inheritance

UUID: 1d1c6414-89d7-42c8-85d3-38f95b02cc08

Approved on: 2023-08-10

Published on: 2023-08-10

HGVS expressions

NM_004360.4:c.892G>A
NM_004360.4(CDH1):c.892G>A (p.Ala298Thr)
NC_000016.10:g.68811743G>A
CM000678.2:g.68811743G>A
NC_000016.9:g.68845646G>A
CM000678.1:g.68845646G>A
NC_000016.8:g.67403147G>A
NG_008021.1:g.79452G>A
ENST00000261769.10:c.892G>A
ENST00000261769.9:c.892G>A
ENST00000422392.6:c.892G>A
ENST00000561751.1:n.514G>A
ENST00000562836.5:n.963G>A
ENST00000566510.5:c.736G>A
ENST00000566612.5:c.892G>A
ENST00000611625.4:c.892G>A
ENST00000612417.4:c.892G>A
ENST00000621016.4:c.892G>A
NM_004360.3:c.892G>A
NM_001317184.1:c.892G>A
NM_001317185.1:c.-724G>A
NM_001317186.1:c.-928G>A
NM_004360.5:c.892G>A
NM_001317184.2:c.892G>A
NM_001317185.2:c.-724G>A
NM_001317186.2:c.-928G>A
NM_004360.5(CDH1):c.892G>A (p.Ala298Thr)

Benign

• Met criteria codes: BS2 BS1

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

Expert Panel

Criteria Specification Information

Criteria Specification: ClinGen CDH1 Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines Version 3.1

Evidence submitted by expert panel

CDH1 VCEP

The c.892G>A (p.Ala298Thr) variant has an allele frequency of 0.00133 (0.1%, 41/30,782 alleles) in the South Asian subpopulation of the gnomAD cohort (BS1). This variant has also been observed in >10 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): BS1, BS2.

Met criteria codes

• BS2: Proband siblings are unaffected carriers. About 300 hets in house, none have DGC.
• BS1: Frequency in South Asian population is 0.13% with 41 alleles.

Not Met criteria codes

• BS4: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• BS3: Functional studies have uncertain clinical relevance.
• 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: Functional studies have uncertain clinical relevance.
• PVS1: 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
• BP1: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• BP4: REVEL shows that computational evidence doesn't meet impact threshold, but evidence is mixed.
• 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
• BA1: Frequency in South Asian population is 0.13% with 41 alleles.
• PP4: Does not meet CDH1 criteria due to high frequency of variant.
• PP2: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PP3: REVEL shows that computational evidence doesn't meet impact threshold, but evidence is mixed.
• 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
• PM2: Frequency in South Asian population is 0.13% with 41 alleles.
• 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