NM_004360.5(CDH1):c.2398del (p.Arg800fs) AND CDH1-related diffuse gastric and lobular breast cancer syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Aug 29, 2023
Review status:: 3 stars out of maximum of 4 stars
reviewed by expert panel

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV003328239.2

Allele description [Variation Report for NM_004360.5(CDH1):c.2398del (p.Arg800fs)]

NM_004360.5(CDH1):c.2398del (p.Arg800fs)

Gene:

CDH1:cadherin 1 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

16q22.1

Genomic location:

Preferred name:

NM_004360.5(CDH1):c.2398del (p.Arg800fs)

Other names:

NM_004360.4(CDH1):c.2398delC

HGVS:

NC_000016.10:g.68829756del
NG_008021.1:g.97465del
NM_001317184.2:c.2215del
NM_001317185.2:c.850del
NM_001317186.2:c.433del
NM_004360.5:c.2398delMANE SELECT
NP_001304113.1:p.Arg739fs
NP_001304114.1:p.Arg284fs
NP_001304115.1:p.Arg145fs
NP_004351.1:p.Arg800fs
LRG_301t1:c.2398del
LRG_301:g.97465del
NC_000016.10:g.68829756delC
NC_000016.9:g.68863656del
NC_000016.9:g.68863659del
NM_004360.3:c.2398del
NM_004360.3:c.2398delC

Protein change:

R145fs

Links:

dbSNP: rs587783048

NCBI 1000 Genomes Browser:

rs587783048

Molecular consequence:

NM_001317184.2:c.2215del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001317185.2:c.850del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001317186.2:c.433del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_004360.5:c.2398del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: CDH1-related diffuse gastric and lobular breast cancer syndrome
Synonyms:: CDH1-related diffuse gastric and lobular breast cancer
Identifiers:: MONDO: MONDO:0100488; MedGen: CN311521

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Gm7205 predicted gene 7205 [Mus musculus]
Gm7205 predicted gene 7205 [Mus musculus]
Gene ID:637307

Gene
D5Mit81 AND (alive[prop]) (1)
Gene
SLC2A4 [Ochotona princeps]
SLC2A4 [Ochotona princeps]
Gene ID:101535491

Gene
HAS3 [Pteropus alecto]
HAS3 [Pteropus alecto]
Gene ID:102887158

Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000864588	ClinGen CDH1 Variant Curation Expert Panel	reviewed by expert panel (ClinGen CDH1 ACMG Specifications V3.1)	Pathogenic (Aug 29, 2023)	germline	curation	PubMed (2) [See all records that cite these PMIDs] 18427545, 17545690 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000864588

ClinGen CDH1 Variant Curation Expert Panel

reviewed by expert panel

(ClinGen CDH1 ACMG Specifications V3.1)

Pathogenic
(Aug 29, 2023)

germline

curation

PubMed (2)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	curation

Citations

PubMed

The NMD mRNA surveillance pathway downregulates aberrant E-cadherin transcripts in gastric cancer cells and in CDH1 mutation carriers.

Karam R, Carvalho J, Bruno I, Graziadio C, Senz J, Huntsman D, Carneiro F, Seruca R, Wilkinson MF, Oliveira C.

Oncogene. 2008 Jul 10;27(30):4255-60. doi: 10.1038/onc.2008.62. Epub 2008 Apr 21.

PubMed [citation]

PMID:: 18427545

Founder and recurrent CDH1 mutations in families with hereditary diffuse gastric cancer.

Kaurah P, MacMillan A, Boyd N, Senz J, De Luca A, Chun N, Suriano G, Zaor S, Van Manen L, Gilpin C, Nikkel S, Connolly-Wilson M, Weissman S, Rubinstein WS, Sebold C, Greenstein R, Stroop J, Yim D, Panzini B, McKinnon W, Greenblatt M, Wirtzfeld D, et al.

JAMA. 2007 Jun 6;297(21):2360-72. Epub 2007 Jun 3.

PubMed [citation]

PMID:: 17545690

Details of each submission

From ClinGen CDH1 Variant Curation Expert Panel, SCV000864588.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	curation	PubMed (2)

Description

The c.2398delC (p.Arg800Alafs*16) variant is predicted to result in a premature stop codon that leads to a truncated protein. However, it is located within the nonsense mediated decay resistance region upstream of c.2506G>T (p.Glu836*) (PVS1_Strong). The variant is absent in the gnomAD cohort (PM2_Supporting; http://gnomad.broadinstitute.org). This variant has been reported in at least 4 families meeting HDGC clinical criteria (PS4; PMID 17545690). This variant was also found to co-segregation with disease in multiple affected family members, with 3 or 4 meioses observed (PP1; PMID: 17545690). In summary, 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 (Variant Interpretation Guidelines Version 3.1): PVS1_Strong, PM2_Supporting, PS4, PP1.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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