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NM_004360.5(CDH1):c.2474dup (p.Pro826fs) AND CDH1-related diffuse gastric and lobular breast cancer syndrome

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Aug 2, 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:
RCV003328412.1

Allele description [Variation Report for NM_004360.5(CDH1):c.2474dup (p.Pro826fs)]

NM_004360.5(CDH1):c.2474dup (p.Pro826fs)

Gene:
CDH1:cadherin 1 [Gene - OMIM - HGNC]
Variant type:
Duplication
Cytogenetic location:
16q22.1
Genomic location:
Preferred name:
NM_004360.5(CDH1):c.2474dup (p.Pro826fs)
Other names:
NM_004360.5(CDH1):c.2474dup; p.Pro826fs
HGVS:
  • NC_000016.10:g.68833324dup
  • NG_008021.1:g.101033dup
  • NM_001317184.2:c.2291dup
  • NM_001317185.2:c.926dup
  • NM_001317186.2:c.509dup
  • NM_004360.5:c.2474dupMANE SELECT
  • NP_001304113.1:p.Pro765fs
  • NP_001304114.1:p.Pro310fs
  • NP_001304115.1:p.Pro171fs
  • NP_004351.1:p.Pro826fs
  • LRG_301t1:c.2474dup
  • LRG_301:g.101033dup
  • NC_000016.9:g.68867223_68867224insC
  • NC_000016.9:g.68867227dup
  • NM_004360.3:c.2474dup
  • NM_004360.3:c.2474dupC
Protein change:
P171fs
Links:
dbSNP: rs1555518221
NCBI 1000 Genomes Browser:
rs1555518221
Molecular consequence:
  • NM_001317184.2:c.2291dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001317185.2:c.926dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001317186.2:c.509dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_004360.5:c.2474dup - 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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Assertion and evidence details

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Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004035081ClinGen CDH1 Variant Curation Expert Panel
reviewed by expert panel

(ClinGen CDH1 ACMG Specifications V3.1)		Pathogenic
(Aug 2, 2023) 		germlinecuration

Citation Link

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Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedcuration

Details of each submission

From ClinGen CDH1 Variant Curation Expert Panel, SCV004035081.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcurationnot provided

Description

The NM_004360.5:c.2474dup (p.Pro826AlafsTer3) variant in CDH1 is a frameshift variant that may cause a premature stop codon that is predicted to escape nonsense mediated decay. However, this truncated region (removes last 57 amino acids of the protein) is critical to protein function and located upstream the most 3' well-characterized pathogenic variant c.2506G>T (pGlu836Ter) (PVS1_Strong, PM5_Supporting; PMID: 29798843, ClinVar Variation ID: 479504). This variant is absent in gnomAD 2.1.1 (PM2_Supporting). This variant has been reported in 5 families meeting HDGC criteria (PS4; NCI hereditary gastric study, Ambry, Invitae). In summary, this variant meets the criteria to be classified as pathogenic for DGLBCS based on the ACMG/AMP criteria applied, as specified by the ClinGen CDH1 VCEP: PVS1_Strong, PS4, PM2_Supporting, PM5_Supporting. (CDH1 VCEP specifications version 3.1; 5/6/2022)

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024