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NM_004360.5(CDH1):c.2506G>T (p.Glu836Ter) AND CDH1-related diffuse gastric and lobular breast cancer syndrome

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Aug 29, 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:
RCV003328405.4

Allele description [Variation Report for NM_004360.5(CDH1):c.2506G>T (p.Glu836Ter)]

NM_004360.5(CDH1):c.2506G>T (p.Glu836Ter)

Gene:
CDH1:cadherin 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
16q22.1
Genomic location:
Preferred name:
NM_004360.5(CDH1):c.2506G>T (p.Glu836Ter)
Other names:
NM_004360.4(CDH1):c.2506G>T
HGVS:
  • NC_000016.10:g.68833356G>T
  • NG_008021.1:g.101065G>T
  • NM_001317184.2:c.2323G>T
  • NM_001317185.2:c.958G>T
  • NM_001317186.2:c.541G>T
  • NM_004360.5:c.2506G>TMANE SELECT
  • NP_001304113.1:p.Glu775Ter
  • NP_001304114.1:p.Glu320Ter
  • NP_001304115.1:p.Glu181Ter
  • NP_004351.1:p.Glu836Ter
  • LRG_301t1:c.2506G>T
  • LRG_301:g.101065G>T
  • NC_000016.9:g.68867259G>T
  • NM_004360.3:c.2506G>T
Protein change:
E181*
Links:
dbSNP: rs1555518239
NCBI 1000 Genomes Browser:
rs1555518239
Molecular consequence:
  • NM_001317184.2:c.2323G>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001317185.2:c.958G>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001317186.2:c.541G>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_004360.5:c.2506G>T - nonsense - [Sequence Ontology: SO:0001587]

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
SCV000864582ClinGen CDH1 Variant Curation Expert Panel
reviewed by expert panel

(ClinGen CDH1 ACMG Specifications V3.1)		Pathogenic
(Aug 29, 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, SCV000864582.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcurationnot provided

Description

The c.2506G>T (p.Glu836*) variant results in a premature stop codon that leads to a truncated protein. While it is located within the nonsense mediated decay resistance region,it is recognized as the most c-terminal pathogenic variant in CDH1 (PVS1_Strong, PMID: 29798843). This variant is absent in the gnomAD cohort (PM2_Supporting; http://gnomad.broadinstitute.org). There is one known de novo observation with parental confirmation in a patient with diffuse gastric cancer and/or lobular breast cancer (PS2; PMID: 29798843). In summary, this variant meets criteria to be classified as likely pathogenic based on the ACMG/AMP criteria applied as specified by the CDH1 Variant Curation Expert Panel: PVS1_Strong, PM2_Supporting, PS2.

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

Last Updated: Oct 26, 2024