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NM_004360.5(CDH1):c.1565+1G>C AND CDH1-related diffuse gastric and lobular breast cancer syndrome

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Aug 28, 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:
RCV003328341.2

Allele description [Variation Report for NM_004360.5(CDH1):c.1565+1G>C]

NM_004360.5(CDH1):c.1565+1G>C

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.1565+1G>C
HGVS:
  • NC_000016.10:g.68815760G>C
  • NG_008021.1:g.83469G>C
  • NM_001317184.2:c.1382+1G>C
  • NM_001317185.2:c.17+1G>C
  • NM_001317186.2:c.-255+1G>C
  • NM_004360.5:c.1565+1G>CMANE SELECT
  • LRG_301t1:c.1565+1G>C
  • LRG_301:g.83469G>C
  • NC_000016.9:g.68849663G>C
  • NM_004360.3:c.1565+1G>C
Links:
dbSNP: rs587780113
NCBI 1000 Genomes Browser:
rs587780113
Molecular consequence:
  • NM_001317184.2:c.1382+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001317185.2:c.17+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001317186.2:c.-255+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_004360.5:c.1565+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]

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
SCV001943330ClinGen CDH1 Variant Curation Expert Panel
reviewed by expert panel

(ClinGen CDH1 ACMG Specifications V3.1)		Pathogenic
(Aug 28, 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, SCV001943330.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcurationnot provided

Description

The c.1565+1G>C variant is a canonical splice variant predicted to result in a truncated or absent protein (PVS1_Strong, PM5_Supporting). The variant is absent in the gnomAD cohort (PM2_Supporting; http://gnomad.broadinstitute.org). This variant has been reported in at least four families meeting HDGC clinical criteria (PS4; PMID: 26182300, SCV000545383.5 and internal laboratory contributor). This variant was also found to co-segregate with disease in multiple affected family members, with at least nine meioses observed across four families (PP1_Strong; SCV000545383.5, SCV000665081.3 and internal laboratory contributor). In summary, this variant meets criteria to be classified as pathogenic based on the ACMG/AMP criteria applied as specified by the CDH1 Variant Curation Expert Panel (Variant Interpretation Guidelines Version 3.1): PVS1_Strong, PS4, PP1_Strong, PM2_Supporting, PM5_Supporting.

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

Last Updated: Sep 29, 2024