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]

Variant: NM_004360.5(CDH1):c.2287G>T (p.Glu763Ter)

CA332835

136065 (ClinVar)

Gene: CDH1
Condition: CDH1-related diffuse gastric and lobular breast cancer
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: a37a7b3b-eda4-4ed2-8848-63a6ca3f3aa5
Approved on: 2023-08-25
Published on: 2023-08-25

HGVS expressions

NM_004360.5:c.2287G>T
NM_004360.5(CDH1):c.2287G>T (p.Glu763Ter)
NC_000016.10:g.68828296G>T
CM000678.2:g.68828296G>T
NC_000016.9:g.68862199G>T
CM000678.1:g.68862199G>T
NC_000016.8:g.67419700G>T
NG_008021.1:g.96005G>T
ENST00000261769.10:c.2287G>T
ENST00000261769.9:c.2287G>T
ENST00000422392.6:c.2104G>T
ENST00000562118.1:n.505G>T
ENST00000562836.5:n.2358G>T
ENST00000566510.5:c.*953G>T
ENST00000566612.5:c.*527G>T
ENST00000611625.4:c.2350G>T
ENST00000612417.4:c.1853+1742G>T
ENST00000621016.4:c.1866-5907G>T
NM_004360.3:c.2287G>T
NM_001317184.1:c.2104G>T
NM_001317185.1:c.739G>T
NM_001317186.1:c.322G>T
NM_004360.4:c.2287G>T
NM_001317184.2:c.2104G>T
NM_001317185.2:c.739G>T
NM_001317186.2:c.322G>T
More

Pathogenic

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

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.2287G>T (p.Glu763Ter) variant results in a premature translational stop signal within the NMD competent region (PVS1, PM5_Supporting). It is absent in the gnomAD cohort (PM2_Supporting; http://https://gnomad.broadinstitute.org/). The variant has been reported in a family meeting HDGC criteria (PMID: 20373070), an individual with signet ring cell carcinoma diagnosed at 33 years of age (PMID: 15138207), and four individuals with DGC (2 <40 years, 2 > 40 years; PMID: 29589180). These reports are mostly out of New Zealand and it is unclear if the reported individuals are all part of a larger kindred (PS4_Supporting). 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
This variant results in a premature translational stop signal (p.Glu763*) within the NMD competent region.
PM5_Supporting
Apply PM5_Supporting to nonsense/frameshift variants that are predicted/proved to undergo NMD.
PM2_Supporting
variant not present in gnomAD or ExAC population databases
PS4_Supporting
The variant has been reported in a family meeting HDGC criteria (PMID: 20373070), an individual with signet ring cell carcinoma diagnosed at 33 years of age (PMID: 15138207), and four individuals with DGC (2 <40 years, 2 > 40 years; PMID: 29589180). These reports are mostly out of New Zealand and it is unclear if the reported individuals are all part of a larger kindred.
Not Met criteria codes
BA1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS1
LOF variant
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
PP3
LOF variant
PP2
LOF variant
PP1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP4
Use PS4 in place of PP4
PM4
variant introduces premature stop codon
PM3
dominant disorder
PM1
Do not use for this gene
PM6
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
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
BP3
variant introduces premature stop codon
BP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP4
LOF variant
BP1
LOF variant
BP7
variant introduces premature stop codon
BP5
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Curation History
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.