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_004360.4(CDH1):c.2549_2550delCC (p.Ser850Phefs)

CA166884

141951 (ClinVar)

Gene: CDH1
Condition: CDH1-related diffuse gastric and lobular breast cancer
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: d170d032-2b2a-4b4c-930b-07c0d30139ca
Approved on: 2023-08-04
Published on: 2023-08-04

HGVS expressions

NM_004360.4:c.2549_2550del
NM_004360.4(CDH1):c.2549_2550delCC (p.Ser850Phefs)
NC_000016.10:g.68833399_68833400del
CM000678.2:g.68833399_68833400del
NC_000016.9:g.68867302_68867303del
CM000678.1:g.68867302_68867303del
NC_000016.8:g.67424803_67424804del
NG_008021.1:g.101108_101109del
ENST00000261769.10:c.2549_2550del
ENST00000261769.9:c.2549_2550del
ENST00000422392.6:c.2366_2367del
ENST00000562118.1:n.767_768del
ENST00000562836.5:n.2620_2621del
ENST00000566510.5:c.*1215_*1216del
ENST00000566612.5:c.*789_*790del
ENST00000611625.4:c.2612_2613del
ENST00000612417.4:c.1854-792_1854-791del
ENST00000621016.4:c.1866-804_1866-803del
NM_004360.3:c.2549_2550del
NM_001317184.1:c.2366_2367del
NM_001317185.1:c.1001_1002del
NM_001317186.1:c.584_585del
NM_004360.5:c.2549_2550del
NM_001317184.2:c.2366_2367del
NM_001317185.2:c.1001_1002del
NM_001317186.2:c.584_585del
NM_004360.5(CDH1):c.2549_2550del (p.Ser850fs)

Uncertain Significance

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

Evidence Links 1

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.2549_2550delCC (p.Ser850PhefsTer10) 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
PVS1_Moderate
A 2 bp deletion in the last exon predicted to result in a premature termination codon in the NMD-resistant zone, downstream of codon 836
PM2_Supporting
Absent in gnomAD
Not Met criteria codes
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
BS2
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
PS4
No reported cases that meet HDGC clinical criteria.
Family does not meet HDGC clinical criteria. Proband with bilateral/contralateral DCIS and IDC/ILC <50, and adenomatous polyps. Same case that has been submitted to ClinVar (SCV000185568.5). PubMed:29798843
PS2
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
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
PM6
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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