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_004360.5(CDH1):c.489C>A (p.Cys163Ter)

CA16620236

420004 (ClinVar)

Gene: CDH1
Condition: CDH1-related diffuse gastric and lobular breast cancer
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 16aa3ae6-e72f-4623-bd36-e264690dbee1
Approved on: 2023-08-25
Published on: 2023-08-25

HGVS expressions

NM_004360.5:c.489C>A
NM_004360.5(CDH1):c.489C>A (p.Cys163Ter)
NC_000016.10:g.68808525C>A
CM000678.2:g.68808525C>A
NC_000016.9:g.68842428C>A
CM000678.1:g.68842428C>A
NC_000016.8:g.67399929C>A
NG_008021.1:g.76234C>A
ENST00000261769.10:c.489C>A
ENST00000261769.9:c.489C>A
ENST00000422392.6:c.489C>A
ENST00000561751.1:n.256C>A
ENST00000562836.5:n.560C>A
ENST00000564676.5:n.771C>A
ENST00000564745.1:n.484C>A
ENST00000566510.5:c.489C>A
ENST00000566612.5:c.489C>A
ENST00000611625.4:c.489C>A
ENST00000612417.4:c.489C>A
ENST00000621016.4:c.489C>A
NM_004360.3:c.489C>A
NM_001317184.1:c.489C>A
NM_001317185.1:c.-1127C>A
NM_001317186.1:c.-1331C>A
NM_004360.4:c.489C>A
NM_001317184.2:c.489C>A
NM_001317185.2:c.-1127C>A
NM_001317186.2:c.-1331C>A

Pathogenic

Met criteria codes 4
PVS1 PS4_Supporting PM5_Supporting PM2_Supporting
Not Met criteria codes 22
BS4 BS3 BS1 BS2 BP5 BP7 BP2 BP3 BP4 BP1 PS2 PS3 PS1 BA1 PP1 PP4 PP3 PP2 PM6 PM3 PM1 PM4

Evidence Links 2

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.489C>A (p.Cys163Ter) variant is predicted to result in a premature stop codon that leads to a truncated or absent protein (PVS1, PM5_Supporting). This 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; PMID 26072394). 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
PVS1
Creates premature termination codon in exon 4 (of 16), which is predicted to lead to loss/truncation of protein.
PS4_Supporting
One family that meets HDGC criteria: 2 GC cases in a family, regardless of age, at least one confirmed DGC, or personal/family history of DGC and LBC; one diagnosed <50 years (PMID: 26072394)
One family that meets HDGC clinical criteria. Proband diagnosed with DGC, LBC, DCIS all under 50, and two first-degree relatives diagnosed with GC (1 is confirmed DGC). This is the same family reported in Kluitj et al 2012 (PMID: 22020549) PubMed:26072394
PM5_Supporting
Apply PM5_Supporting to nonsense/frameshift variants that are predicted/proved to undergo NMD.
PM2_Supporting
Absent in gnomAD v2.1.1
Not Met criteria codes
BS4
One family that meets HDGC criteria, with the following carriers: index 'sister' affected with DGC, healthy 'sister', a healthy 'granddaughter', and her 'son' with cleft lip/palate. PubMed:22020549
BS3
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
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
BP2
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
PS2
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
PS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BA1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP1
A family with no informative affected meioses (PMID: 22020549)
One family that meets HDGC criteria, with the following carriers: index 'sister' affected with DGC, healthy 'sister', a healthy 'granddaughter', and her 'son' with cleft lip/palate. PubMed:22020549
PP4
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
PM6
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
PM4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.
¤ Powered by BCM's Genboree.