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.2505_2506dup (p.Glu836fs)

CA658658500

481173 (ClinVar)

Gene: CDH1
Condition: CDH1-related diffuse gastric and lobular breast cancer
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 9221784c-01b8-448f-9716-33b57bc4c7f0
Approved on: 2023-08-04
Published on: 2023-08-04

HGVS expressions

NM_004360.5:c.2505_2506dup
NM_004360.5(CDH1):c.2505_2506dup
NM_004360.5(CDH1):c.2505_2506dup (p.Glu836fs)
NC_000016.10:g.68833355_68833356dup
CM000678.2:g.68833355_68833356dup
NC_000016.9:g.68867258_68867259dup
CM000678.1:g.68867258_68867259dup
NC_000016.8:g.67424759_67424760dup
NG_008021.1:g.101064_101065dup
ENST00000261769.10:c.2505_2506dup
ENST00000261769.9:c.2505_2506dup
ENST00000422392.6:c.2322_2323dup
ENST00000562118.1:n.723_724dup
ENST00000562836.5:n.2576_2577dup
ENST00000566510.5:c.*1171_*1172dup
ENST00000566612.5:c.*745_*746dup
ENST00000611625.4:c.2568_2569dup
ENST00000612417.4:c.1854-836_1854-835dup
ENST00000621016.4:c.1866-848_1866-847dup
NM_004360.3:c.2505_2506dup
NM_001317184.1:c.2322_2323dup
NM_001317185.1:c.957_958dup
NM_001317186.1:c.540_541dup
NM_004360.4:c.2505_2506dup
NM_001317184.2:c.2322_2323dup
NM_001317185.2:c.957_958dup
NM_001317186.2:c.540_541dup
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Uncertain Significance

Met criteria codes 2
PVS1_Moderate PM2_Supporting
Not Met criteria codes 24
BP5 BP7 BP2 BP3 BP4 BP1 PS2 PS4 PS3 PS1 PP4 PP1 PP3 PP2 PM6 PM3 PM1 PM4 PM5 BA1 BS2 BS4 BS3 BS1

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.2505_2506dupTG (p.Glu836ValfsTer11) variant results in a premature stop codon that leads to a truncated protein. It is located within the nonsense mediated decay resistant zone, and downstream of codon 836 where the most 3' pathogenic variant in CDH1 terminates (PVS1_Moderate, PMID: 29798843). This variant is absent in the gnomAD cohort (PM2_Supporting; http://gnomad.broadinstitute.org). In summary, the clinical significance of this variant is uncertain based on the ACMG/AMP criteria applied as specified by the CDH1 Variant Curation Expert Panel: PVS1_Moderate, PM2_Supporting.
Met criteria codes
PVS1_Moderate
PTC created in exon 16/16 at position 846 in the NMD-resistant zone, downstream of p.Glu836*
PM2_Supporting
Absent in gnomAD v2.1 & v3 in a region of sufficient coverage
Not Met criteria codes
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
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
PS2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS4
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
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
PM6
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
PM5
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
BS2
1 individual w/o DGC, SRC tumors, or LBC & whose families do not suggest HDGC
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
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Curation History
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