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.1131del (p.Thr378fs)

CA645369682

428623 (ClinVar)

Gene: CDH1
Condition: CDH1-related diffuse gastric and lobular breast cancer
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: f51729c7-8a69-436a-9f07-26150679b088
Approved on: 2023-08-25
Published on: 2023-08-25

HGVS expressions

NM_004360.5:c.1131del
NM_004360.5(CDH1):c.1131del (p.Thr378fs)
NC_000016.10:g.68812257del
CM000678.2:g.68812257del
NC_000016.9:g.68846160del
CM000678.1:g.68846160del
NC_000016.8:g.67403661del
NG_008021.1:g.79966del
ENST00000261769.10:c.1131del
ENST00000261769.9:c.1131del
ENST00000422392.6:c.1131del
ENST00000562836.5:n.1202del
ENST00000565810.1:n.175del
ENST00000566510.5:c.975del
ENST00000566612.5:c.1131del
ENST00000611625.4:c.1131del
ENST00000612417.4:c.1131del
ENST00000621016.4:c.1131del
NM_004360.3:c.1131del
NM_001317184.1:c.1131del
NM_001317185.1:c.-485del
NM_001317186.1:c.-689del
NM_004360.4:c.1131del
NM_001317184.2:c.1131del
NM_001317185.2:c.-485del
NM_001317186.2:c.-689del
More

Pathogenic

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

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.1131delC p.(Thr378fs) 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). This variant has been reported in at least one family meeting HDGC clinical criteria (PS4_Supporting; SCV000580700.3). 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
SCV000580700.3 - proband meets the HDGC phenotype criteria.
PVS1
Exon 8 of 16, predicted NMD.
PM5_Supporting
Apply PM5_Supporting to nonsense/frameshift variants that are predicted/proved to undergo NMD.
PM2_Supporting
Absent in population databases.
Not Met criteria codes
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
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
BA1
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
PP1
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
PM6
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
PM3
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
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
Curation History
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