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NM_004360.5(CDH1):c.1568A>G (p.Tyr523Cys) AND CDH1-related diffuse gastric and lobular breast cancer syndrome

Germline classification:
Benign (1 submission)
Last evaluated:
Aug 3, 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:
RCV003328207.1

Allele description [Variation Report for NM_004360.5(CDH1):c.1568A>G (p.Tyr523Cys)]

NM_004360.5(CDH1):c.1568A>G (p.Tyr523Cys)

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.1568A>G (p.Tyr523Cys)
Other names:
p.Y523C:TAT>TGT; NM_004360.5(CDH1):c.1568A>G
HGVS:
  • NC_000016.10:g.68819282A>G
  • NG_008021.1:g.86991A>G
  • NM_001317184.2:c.1385A>G
  • NM_001317185.2:c.20A>G
  • NM_001317186.2:c.-254-2719A>G
  • NM_004360.5:c.1568A>GMANE SELECT
  • NP_001304113.1:p.Tyr462Cys
  • NP_001304114.1:p.Tyr7Cys
  • NP_004351.1:p.Tyr523Cys
  • LRG_301t1:c.1568A>G
  • LRG_301:g.86991A>G
  • NC_000016.9:g.68853185A>G
  • NM_004360.3:c.1568A>G
  • NM_004360.4:c.1568A>G
  • p.Y523C
Protein change:
Y462C
Links:
dbSNP: rs553907248
NCBI 1000 Genomes Browser:
rs553907248
Molecular consequence:
  • NM_001317186.2:c.-254-2719A>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001317184.2:c.1385A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001317185.2:c.20A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_004360.5:c.1568A>G - missense variant - [Sequence Ontology: SO:0001583]

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
SCV004035101ClinGen CDH1 Variant Curation Expert Panel
reviewed by expert panel

(ClinGen CDH1 ACMG Specifications V3.1)		Benign
(Aug 3, 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, SCV004035101.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcurationnot provided

Description

The filtering allele frequency of the c.1568A>G (p.Tyr523Cys) variant in the CDH1 gene is 0.15% for Latino/Admixed American chromosomes in gnomAD (95% CI of 23/15282), which meets the allele frequency threshold defined by the ClinGen CDH1 Variant Curation Expert Panel for considering strong evidence against pathogenicity for autosomal dominant hereditary diffuse gastric cancer variants (BS1). This variant has been observed in >10 individuals without a diagnosis of diffuse gastric cancer, signet ring tumor or lobular breast cancer and whose family histories do not suggest HDGC (BS2; internal laboratory contributors). This variant was observed in the homozygous state in 9 individuals without personal and/or family history of DGC, LBC, or SRC tumors (BP2_strong; internal laboratory contributors). In summary, the clinical significance of this variant is classified as benign. ACMG/AMP criteria applied, as specified by the CDH1 Variant Curation Expert Panel: BS1, BS2, BP2_strong. (CDH1 VCEP specifications version 3.1; 06/26/2023)

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

Last Updated: Oct 13, 2024