NM_004360.5(CDH1):c.2490dup (p.Leu831fs) AND Hereditary cancer-predisposing syndrome

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Jul 31, 2015
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:: RCV000492088.4

Allele description [Variation Report for NM_004360.5(CDH1):c.2490dup (p.Leu831fs)]

NM_004360.5(CDH1):c.2490dup (p.Leu831fs)

Gene:

CDH1:cadherin 1 [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

16q22.1

Genomic location:

Preferred name:

NM_004360.5(CDH1):c.2490dup (p.Leu831fs)

Other names:

NM_004360.5(CDH1):c.2490dup; p.Leu831fs

HGVS:

NC_000016.10:g.68833340dup
NG_008021.1:g.101049dup
NM_001317184.2:c.2307dup
NM_001317185.2:c.942dup
NM_001317186.2:c.525dup
NM_004360.5:c.2490dupMANE SELECT
NP_001304113.1:p.Leu770fs
NP_001304114.1:p.Leu315fs
NP_001304115.1:p.Leu176fs
NP_004351.1:p.Leu831fs
LRG_301t1:c.2490dup
LRG_301:g.101049dup
NC_000016.9:g.68867242_68867243insG
NC_000016.9:g.68867243dup
NM_004360.3:c.2490dupG

Protein change:

L176fs

Links:

dbSNP: rs1131690822

NCBI 1000 Genomes Browser:

rs1131690822

Molecular consequence:

NM_001317184.2:c.2307dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001317185.2:c.942dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001317186.2:c.525dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_004360.5:c.2490dup - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Hereditary cancer-predisposing syndrome
Synonyms:: Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000580713	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Likely pathogenic (Jul 31, 2015)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000580713

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Likely pathogenic
(Jul 31, 2015)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

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	clinical testing

Citations

PubMed

Dynamic and static interactions between p120 catenin and E-cadherin regulate the stability of cell-cell adhesion.

Ishiyama N, Lee SH, Liu S, Li GY, Smith MJ, Reichardt LF, Ikura M.

Cell. 2010 Apr 2;141(1):117-28. doi: 10.1016/j.cell.2010.01.017.

PubMed [citation]

PMID:: 20371349

Details of each submission

From Ambry Genetics, SCV000580713.6

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

Description

The c.2490dupG variant, located in coding exon 16 of the CDH1 gene, results from a duplication of G at nucleotide position 2490, and causes a translational frameshift with a predicted alternate stop codon (p.L831Afs*4). Frameshifts are typically deleterious in nature, however, this frameshift occurs at the 3' terminus of CDH1, is not expected to trigger nonsense-mediated mRNA decay, and impacts only the last 52 amino acids of the protein. The exact functional impact of these altered amino acids is unknown at this time; however, the deleted region eliminates the catenin-binding domain, which is important for regulating the stability of cadherin mediated cell-cell adhesion (Ishiyama N et al. Cell 2010 Apr; 141(1):117-28). In addition, this alteration was previously seen in a patient diagnosed with diffuse gastric cancer at 31 (Ambry internal data). Based on the majority of available evidence to date, this variant is likely to be 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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