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]
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Variant: NM_004360.5(CDH1):c.1942G>T (p.Glu648Ter)

CA396467508

463735 (ClinVar)

Gene: CDH1
Condition: CDH1-related diffuse gastric and lobular breast cancer
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: c0b7ca7d-517c-418e-a1e3-22e57e6bd197
Approved on: 2023-08-04
Published on: 2023-08-04

HGVS expressions

NM_004360.5(CDH1):c.1942G>T
NM_004360.5:c.1942G>T
NM_004360.5(CDH1):c.1942G>T (p.Glu648Ter)
NC_000016.10:g.68823404G>T
CM000678.2:g.68823404G>T
NC_000016.9:g.68857307G>T
CM000678.1:g.68857307G>T
NC_000016.8:g.67414808G>T
NG_008021.1:g.91113G>T
ENST00000261769.10:c.1942G>T
ENST00000261769.9:c.1942G>T
ENST00000422392.6:c.1759G>T
ENST00000562118.1:n.160G>T
ENST00000562836.5:n.2013G>T
ENST00000566510.5:c.*608G>T
ENST00000566612.5:c.*182G>T
ENST00000611625.4:c.2005G>T
ENST00000612417.4:c.1830+1285G>T
ENST00000621016.4:c.1865+1250G>T
NM_004360.3:c.1942G>T
NM_001317184.1:c.1759G>T
NM_001317185.1:c.394G>T
NM_001317186.1:c.-24G>T
NM_004360.4:c.1942G>T
NM_001317184.2:c.1759G>T
NM_001317185.2:c.394G>T
NM_001317186.2:c.-24G>T

Pathogenic

Met criteria codes 3
PM2_Supporting PM5_Supporting PVS1
Not Met criteria codes 23
PM6 PM1 PM4 PM3 BS2 BS3 BS4 BS1 BP7 BP5 BP3 BP4 BP1 BP2 PS1 PS3 PS2 PS4 PP3 PP2 PP4 PP1 BA1

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.1942G>T p.(Glu648Ter) variant is predicted to result in a premature stop codon that leads to nonsense mediate decay (PVS1 and PM5_supporting). The variant is absent in the gnomAD cohort (PM2_supporting; http://gnomad.broadinstitute.org). Therefore, 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 (CDH1 VCEP specifications version 3.1): PVS1, PM2_supporting, PM5_supporting.
Met criteria codes
PM2_Supporting
Absent in population databases.
PM5_Supporting
Exon 13 of 16, predicted NMD.
PVS1
Exon 13 of 16, predicted NMD.
Not Met criteria codes
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
2 unaffected probands in 30s (Invitae).
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
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
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
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
PS4
SCV000637759.1 - ILC in 40s (?bilateral). PMID: 24366306 - does not meet HDGC criteria.
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
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
BA1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
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