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.1587dup (p.Ala530fs)

CA16620251

422539 (ClinVar)

Gene: CDH1
Condition: CDH1-related diffuse gastric and lobular breast cancer
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 55e01934-c703-4d75-ae7e-ad1eb3df27e3

HGVS expressions

NM_004360.5:c.1587dup
NM_004360.5(CDH1):c.1587dup (p.Ala530fs)
NC_000016.10:g.68819301dup
CM000678.2:g.68819301dup
NC_000016.9:g.68853204dup
CM000678.1:g.68853204dup
NC_000016.8:g.67410705dup
NG_008021.1:g.87010dup
ENST00000261769.10:c.1587dup
ENST00000261769.9:c.1587dup
ENST00000422392.6:c.1404dup
ENST00000562836.5:n.1658dup
ENST00000566510.5:c.*253dup
ENST00000566612.5:c.1566-2700dup
ENST00000611625.4:c.1650dup
ENST00000612417.4:c.1587dup
ENST00000621016.4:c.1587dup
NM_004360.3:c.1587dup
NM_001317184.1:c.1404dup
NM_001317185.1:c.39dup
NM_001317186.1:c.-254-2700dup
NM_004360.4:c.1587dup
NM_001317184.2:c.1404dup
NM_001317185.2:c.39dup
NM_001317186.2:c.-254-2700dup

Pathogenic

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

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.1587dup (p.Ala530fs) 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://https://gnomad.broadinstitute.org/). This variant has been identified in a family meeting HDGC clinical criteria (PS4_Supporting; SCV000580697.3). 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
PM2_Supporting
Variant not present in gnomAD
PM5_Supporting
Apply PM5_Supporting to nonsense/frameshift variants that are predicted/proved to undergo NMD.
PS4_Supporting
Variant present in female with history of signet cell adenocarcinoma diagnosed @ 20s (SCV000580697.3).
PVS1
Variant creates a premature stop codon at position 7 (amino acid 536) of the new reading frame
Not Met criteria codes
BS2
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
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS1
Variant not present in gnomAD
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
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
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
Variant not present in gnomAD
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
PM6
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
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
Approved on: 2023-08-25
Published on: 2023-08-25
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.