NM_004360.5(CDH1):c.2474del (p.Pro825fs) AND Hereditary diffuse gastric adenocarcinoma

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 21, 2020
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:: RCV000812733.7

Allele description [Variation Report for NM_004360.5(CDH1):c.2474del (p.Pro825fs)]

NM_004360.5(CDH1):c.2474del (p.Pro825fs)

Gene:

CDH1:cadherin 1 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

16q22.1

Genomic location:

Preferred name:

NM_004360.5(CDH1):c.2474del (p.Pro825fs)

HGVS:

NC_000016.10:g.68833324del
NG_008021.1:g.101033del
NM_001317184.2:c.2291del
NM_001317185.2:c.926del
NM_001317186.2:c.509del
NM_004360.5:c.2474delMANE SELECT
NP_001304113.1:p.Pro764fs
NP_001304114.1:p.Pro309fs
NP_001304115.1:p.Pro170fs
NP_004351.1:p.Pro825fs
LRG_301t1:c.2474del
LRG_301:g.101033del
NC_000016.9:g.68867224del
NC_000016.9:g.68867227del
NM_004360.3:c.2474del

Protein change:

P170fs

Links:

dbSNP: rs1555518221

NCBI 1000 Genomes Browser:

rs1555518221

Molecular consequence:

NM_001317184.2:c.2291del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001317185.2:c.926del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001317186.2:c.509del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_004360.5:c.2474del - 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

Macrolide Antibiotics - LiverTox
Macrolide Antibiotics - LiverTox
DSG2-AS1 DSG2 antisense RNA 1 [Homo sapiens]
DSG2-AS1 DSG2 antisense RNA 1 [Homo sapiens]
Gene ID:100652770

Gene
Gene Links for GEO Profiles (Select 78828466) (1)
Gene
Profile neighbors for GEO Profiles (Select 96580633) (183)
GEO Profiles
Chromosome neighbors for GEO Profiles (Select 96580835) (20)
GEO Profiles

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
SCV000953056	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 21, 2020)	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

SCV000953056

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 21, 2020)

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, SCV000953056.4

#	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 the C-terminus of the CDH1 protein. Other variant(s) that disrupt this region (p.Pro826Alafs*3, p.Glu836*) have been determined to be pathogenic (PMID: 29798843, Invitae). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the affected amino acid(s) is currently unknown. This variant has not been reported in the literature in individuals with CDH1-related conditions. ClinVar contains an entry for this variant (Variation ID: 656340). This variant is not present in population databases (ExAC no frequency). This sequence change results in a premature translational stop signal in the CDH1 gene (p.Pro825Argfs*21). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 58 amino acids 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