NM_004360.5(CDH1):c.2490dup (p.Leu831fs) AND Hereditary diffuse gastric adenocarcinoma

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Mar 1, 2022
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:: RCV001712455.4

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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003461741	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Mar 1, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 29798843, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003461741

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Mar 1, 2022)

germline

clinical testing

PubMed (2)
[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

A novel de novo CDH1 germline variant aids in the classification of carboxy-terminal E-cadherin alterations predicted to escape nonsense-mediated mRNA decay.

Krempely K, Karam R.

Cold Spring Harb Mol Case Stud. 2018 Aug 1;4(4). doi:pii: a003012. 10.1101/mcs.a003012. Print 2018 Aug.

PubMed [citation]

PMID:: 29798843
PMCID:: PMC6071572

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003461741.2

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

Description

For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the CDH1 protein in which other variant(s) (p.Glu836*) have been determined to be pathogenic (PMID: 29798843). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 428634). This premature translational stop signal has been observed in individuals with diffuse gastric cancer (PMID: 29798843; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Leu831Alafs*4) in the CDH1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 52 amino acid(s) of the CDH1 protein.

#	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

ClinVar

Relating variation to medicine