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.2505T>G (p.Tyr835Ter)

CA396472208

921477 (ClinVar)

Gene: CDH1
Condition: CDH1-related diffuse gastric and lobular breast cancer
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: e4b09407-f4ff-42aa-8b88-e45bbdd1299f
Approved on: 2023-08-04
Published on: 2023-08-04

HGVS expressions

NM_004360.5:c.2505T>G
NM_004360.5(CDH1):c.2505T>G (p.Tyr835Ter)
NC_000016.10:g.68833355T>G
CM000678.2:g.68833355T>G
NC_000016.9:g.68867258T>G
CM000678.1:g.68867258T>G
NC_000016.8:g.67424759T>G
NG_008021.1:g.101064T>G
ENST00000261769.10:c.2505T>G
ENST00000261769.9:c.2505T>G
ENST00000422392.6:c.2322T>G
ENST00000562118.1:n.723T>G
ENST00000562836.5:n.2576T>G
ENST00000566510.5:c.*1171T>G
ENST00000566612.5:c.*745T>G
ENST00000611625.4:c.2568T>G
ENST00000612417.4:c.1854-836T>G
ENST00000621016.4:c.1866-848T>G
NM_004360.3:c.2505T>G
NM_001317184.1:c.2322T>G
NM_001317185.1:c.957T>G
NM_001317186.1:c.540T>G
NM_004360.4:c.2505T>G
NM_001317184.2:c.2322T>G
NM_001317185.2:c.957T>G
NM_001317186.2:c.540T>G

Likely Pathogenic

Met criteria codes 3
PM2_Supporting PVS1_Strong PM5_Supporting
Not Met criteria codes 23
PM6 PM3 PM1 PM4 BS2 BS4 BS3 BS1 BP5 BP7 BP2 BP3 BP4 BP1 PS2 PS4 PS3 PS1 BA1 PP4 PP1 PP3 PP2

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.2505T>G (p.Tyr835Ter) variant results in a premature translational stop signal upstream of the most 3’ well-characterized pathogenic variant c.2506G>T (p.Glu836Ter) in a region that is not predicted to undergo nonsense-mediated decay (PVS1_Strong, PM5_Supporting). It is absent in the gnomAD cohort (PM2_Supporting; http://https://gnomad.broadinstitute.org/). In summary, this variant meets criteria to be classified as Likely Pathogenic based on the ACMG/AMP criteria applied as specified by the CDH1 Variant Curation Expert Panel: PVS1_Strong, PM2_Supporting, PM5_Supporting. (CDH1 VCEP specifications version 3.1; 03/27/2023)
Met criteria codes
PM2_Supporting
Absent in gnomAD v2.1.1, coverage >30X
PVS1_Strong
Not predicted to undergo NMD, nonsense variant between c.2389-c.2508
PM5_Supporting
PM5_Supporting can be applied to truncating variants located upstream of the last known pathogenic truncating variant [c.2506G>T (p.Glu836Ter)].
Not Met criteria codes
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
BS2
Variant not seen at Ambry, Invitae, GeneDx
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
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
Variant not seen at Ambry, Invitae, GeneDx
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
BA1
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
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