NM_004360.5(CDH1):c.2164+6_2439+966del AND Hereditary diffuse gastric adenocarcinoma

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Mar 12, 2019
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV001048458.2

Allele description [Variation Report for NM_004360.5(CDH1):c.2164+6_2439+966del]

NM_004360.5(CDH1):c.2164+6_2439+966del

Gene:

CDH1:cadherin 1 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

16q22.1

Genomic location:

Preferred name:

NM_004360.5(CDH1):c.2164+6_2439+966del

HGVS:

NC_000016.10:g.68823632_68830763del
NG_008021.1:g.91341_98472del
NM_001317184.2:c.1981+6_2256+966del
NM_001317185.2:c.616+6_891+966del
NM_001317186.2:c.199+6_474+966del
NM_004360.5:c.2164+6_2439+966delMANE SELECT
LRG_301t1:c.2164+6_2439+966del
LRG_301:g.91341_98472del
NC_000016.9:g.68857535_68864666del
NM_004360.3:c.2164+6_2439+966del

Molecular consequence:

NM_001317184.2:c.1981+6_2256+966del - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001317185.2:c.616+6_891+966del - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001317186.2:c.199+6_474+966del - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_004360.5:c.2164+6_2439+966del - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001317184.2:c.1981+6_2256+966del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001317185.2:c.616+6_891+966del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001317186.2:c.199+6_474+966del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_004360.5:c.2164+6_2439+966del - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Name:: Hereditary diffuse gastric adenocarcinoma (HDGC)
Synonyms:: Hereditary diffuse gastric cancer
Identifiers:: MONDO: MONDO:0007648; MedGen: C1708349; Orphanet: 26106; OMIM: 137215

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001212465	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Mar 12, 2019)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 19168852, 22850631, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001212465

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Mar 12, 2019)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

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	clinical testing

Citations

PubMed

Germline CDH1 deletions in hereditary diffuse gastric cancer families.

Oliveira C, Senz J, Kaurah P, Pinheiro H, Sanges R, Haegert A, Corso G, Schouten J, Fitzgerald R, Vogelsang H, Keller G, Dwerryhouse S, Grimmer D, Chin SF, Yang HK, Jackson CE, Seruca R, Roviello F, Stupka E, Caldas C, Huntsman D.

Hum Mol Genet. 2009 May 1;18(9):1545-55. doi: 10.1093/hmg/ddp046. Epub 2009 Jan 24.

PubMed [citation]

PMID:: 19168852
PMCID:: PMC2667284

The importance of E-cadherin binding partners to evaluate the pathogenicity of E-cadherin missense mutations associated to HDGC.

Figueiredo J, Söderberg O, Simões-Correia J, Grannas K, Suriano G, Seruca R.

Eur J Hum Genet. 2013 Mar;21(3):301-9. doi: 10.1038/ejhg.2012.159. Epub 2012 Aug 1.

PubMed [citation]

PMID:: 22850631
PMCID:: PMC3573198

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001212465.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This variant is a sub-genic deletion of the genomic region encompassing exons 14-15 of the CDH1 gene. While this deletion is not anticipated to result in nonsense mediated decay, it is expected to create a truncated protein product. This variant has not been reported in the literature in individuals with CDH1-related conditions. This variant is expected to affect the C-terminal portion of the cytoplasmic domain of the CDH1 (E-cadherin) protein, which includes the binding domains for the PIP5K1C (phosphatidylinositol phosphate kinase, type I gamma) and CTNNB1 (beta-catenin) proteins (PMID: 22850631). Loss of these domains is expected to disrupt normal E-cadherin function. This suggests that deletion of this region of the CDH1 protein is causative of disease. Sub-genic deletion of exons 14-16 and exon 16 have been determined to be pathogenic (PMID: PMID: 19168852, Invitae). Therefore, deletions that fully encompass that region are also expected to be pathogenic. For these reasons, this variant has been classified as Pathogenic.

#	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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