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]
Link to SEPIO compliant JSON-LD document

Variant: NM_004360.5(CDH1):c.2547_2548insA (p.Ser850fs)

CA10577553

234904 (ClinVar)

Gene: CDH1
Condition: CDH1-related diffuse gastric and lobular breast cancer
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: bbd057d3-ccf7-434b-bc14-d9985ed8087a
Approved on: 2023-08-04
Published on: 2023-08-04

HGVS expressions

NM_004360.5:c.2547_2548insA
NM_004360.5(CDH1):c.2547_2548insA (p.Ser850fs)
NC_000016.10:g.68833397_68833398insA
CM000678.2:g.68833397_68833398insA
NC_000016.9:g.68867300_68867301insA
CM000678.1:g.68867300_68867301insA
NC_000016.8:g.67424801_67424802insA
NG_008021.1:g.101106_101107insA
ENST00000261769.10:c.2547_2548insA
ENST00000261769.9:c.2547_2548insA
ENST00000422392.6:c.2364_2365insA
ENST00000562118.1:n.765_766insA
ENST00000562836.5:n.2618_2619insA
ENST00000566510.5:c.*1213_*1214insA
ENST00000566612.5:c.*787_*788insA
ENST00000611625.4:c.2610_2611insA
ENST00000612417.4:c.1854-794_1854-793insA
ENST00000621016.4:c.1866-806_1866-805insA
NM_004360.3:c.2547_2548insA
NM_001317184.1:c.2364_2365insA
NM_001317185.1:c.999_1000insA
NM_001317186.1:c.582_583insA
NM_004360.4:c.2547_2548insA
NM_001317184.2:c.2364_2365insA
NM_001317185.2:c.999_1000insA
NM_001317186.2:c.582_583insA

Uncertain Significance

Met criteria codes 2
PM2_Supporting PVS1_Moderate
Not Met criteria codes 24
PP4 PP1 PP3 PP2 PM6 PM3 PM4 PM1 PM5 PS3 PS2 PS4 PS1 BA1 BP7 BP5 BP2 BP3 BP4 BP1 BS2 BS3 BS4 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.2547_2548insA (p.Ser850IlefsTer11) 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 (CDH1 VCEP specifications version 3.1): PVS1_Moderate, PM2_Supporting.
Met criteria codes
PM2_Supporting
Absent in gnomAD v2.1 & v3 in a region of sufficient coverage
PVS1_Moderate
PTC created in exon 16/16 at position 860 in the NMD-resistant zone, downstream of p.Glu836* (p.Ser850Ilefs*11)
Not Met criteria codes
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
PM4
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
PM5
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
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
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
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
BS2
1 individual w/o DGC, SRC tumors, or LBC & whose families do not suggest HDGC
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
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