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_004360.4(CDH1):c.1147C>T (p.Gln383Ter)

CA169687

142888 (ClinVar)

Gene: CDH1
Condition: CDH1-related diffuse gastric and lobular breast cancer
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 85e6ec9e-bbed-4967-a6af-72d3f6999902
Approved on: 2023-08-25
Published on: 2023-08-25

HGVS expressions

NM_004360.4:c.1147C>T
NM_004360.4(CDH1):c.1147C>T (p.Gln383Ter)
NC_000016.10:g.68813322C>T
CM000678.2:g.68813322C>T
NC_000016.9:g.68847225C>T
CM000678.1:g.68847225C>T
NC_000016.8:g.67404726C>T
NG_008021.1:g.81031C>T
ENST00000261769.10:c.1147C>T
ENST00000261769.9:c.1147C>T
ENST00000422392.6:c.1137+1059C>T
ENST00000562836.5:n.1218C>T
ENST00000565810.1:n.191C>T
ENST00000566510.5:c.991C>T
ENST00000566612.5:c.1147C>T
ENST00000611625.4:c.1147C>T
ENST00000612417.4:c.1147C>T
ENST00000621016.4:c.1147C>T
NM_004360.3:c.1147C>T
NM_001317184.1:c.1137+1059C>T
NM_001317185.1:c.-469C>T
NM_001317186.1:c.-673C>T
NM_004360.5:c.1147C>T
NM_001317184.2:c.1137+1059C>T
NM_001317185.2:c.-469C>T
NM_001317186.2:c.-673C>T
NM_004360.5(CDH1):c.1147C>T (p.Gln383Ter)
More

Pathogenic

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

Evidence Links 1

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.1147C>T (p.Gln383Ter) 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 23709761). 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
Absent in gnomAD
PS4_Supporting
One French family that meets HDGC clinical criteria. Two DGCs in family, one of them < age 50 (PMID: 23709761). One family that does not meet HDGC clinical criteria, with an index case with ductal breast cancer age 36 (DOI: 10.1200/PO.16.00021 JCO Precision Oncology - published online March 29, 2017).
French index case with DGC dx age 24 and a family member dx with DGC age 43. PubMed:23709761
PM5_Supporting
Apply PM5_Supporting to nonsense/frameshift variants that are predicted/proved to undergo NMD.
PVS1
Predicted null variant in exon 9 of 16. Protein is expected to undergo NMD.
Not Met criteria codes
BA1
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
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
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
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
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
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.