Variant: NM_004360.4(CDH1):c.220C>T (p.Arg74Ter)

CA10583404

239891 (ClinVar)

Gene: CDH1

Condition: CDH1-related diffuse gastric and lobular breast cancer

Inheritance Mode: Autosomal dominant inheritance

UUID: 8e4651fc-c286-49aa-95c4-13401d26f84a

Approved on: 2023-08-29

Published on: 2023-08-29

HGVS expressions

NM_004360.4:c.220C>T
NM_004360.4(CDH1):c.220C>T (p.Arg74Ter)
NC_000016.10:g.68801726C>T
CM000678.2:g.68801726C>T
NC_000016.9:g.68835629C>T
CM000678.1:g.68835629C>T
NC_000016.8:g.67393130C>T
NG_008021.1:g.69435C>T
ENST00000261769.10:c.220C>T
ENST00000261769.9:c.220C>T
ENST00000422392.6:c.220C>T
ENST00000562836.5:n.291C>T
ENST00000564676.5:n.502C>T
ENST00000564745.1:n.215C>T
ENST00000566510.5:c.220C>T
ENST00000566612.5:c.220C>T
ENST00000611625.4:c.220C>T
ENST00000612417.4:c.220C>T
ENST00000621016.4:c.220C>T
NM_004360.3:c.220C>T
NM_001317184.1:c.220C>T
NM_001317185.1:c.-1396C>T
NM_001317186.1:c.-1600C>T
NM_004360.5:c.220C>T
NM_001317184.2:c.220C>T
NM_001317185.2:c.-1396C>T
NM_001317186.2:c.-1600C>T
NM_004360.5(CDH1):c.220C>T (p.Arg74Ter)

Pathogenic

• Met criteria codes: PS4_Supporting PVS1 PM5_Supporting PM2_Supporting

• Not Met criteria codes: BA1 BP7 BP5 BP3 BP4 BP1 BP2 BS3 BS4 BS1 BS2 PP3 PP2 PP4 PP1 PM6 PS1 PS3 PS2 PM4 PM1 PM3

Expert Panel

CDH1 VCEP

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.220C>T p.(Arg74Ter) variant is predicted to result in a premature stop codon that leads to a truncated or absent protein (PVS1, PM5_Supporting). The variant is absent in the gnomAD cohort (PM2_Supporting; http://gnomad.broadinstitute.org). The variant has been reported in at least one family meeting HDGC clinical criteria (PS4_Supporting; SCV000288456.3). In summary, this variant meets criteria to be classified as pathogenic based on the ACMG/AMP criteria applied as specified by the CDH1 Variant Curation Expert Panel (Variant Interpretation Guidelines Version 3.1): PVS1, PM2_Supporting, PS4_supporting, PM5_Supporting.

Met criteria codes

• PS4_Supporting: Found in one individual (76 yo) with gastric adenocarcinoma with suspected family history of gastric cancer (mother, brother), but NOT germline. SCV000288456.3 - one proband meet IGCLC HDGC criteria. - one proband does not meet IGCLC HDGC criteria. SCV000661607.2 - 3 cases do not meet HDGC criteria with unknown pathology.
• PVS1: Predicted NMD.
• PM5_Supporting: Apply PM5_Supporting to nonsense/frameshift variants that are predicted/proved to undergo NMD.
• PM2_Supporting: Not observed in population database.

Not Met criteria codes

• BA1: 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
• BP3: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• BP4: 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
• BS3: 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
• BS1: 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
• PP3: 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
• 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
• PM6: 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: 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
• PM4: 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