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NM_004360.5(CDH1):c.1565+1G>C AND Hereditary cancer-predisposing syndrome

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Feb 23, 2023
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:
RCV000565032.6

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:
Hereditary cancer-predisposing syndrome
Synonyms:
Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000665081Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Pathogenic
(Feb 23, 2023) 		germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Novel germline CDH1 mutations in hereditary diffuse gastric cancer families.

Humar B, Toro T, Graziano F, Müller H, Dobbie Z, Kwang-Yang H, Eng C, Hampel H, Gilbert D, Winship I, Parry S, Ward R, Findlay M, Christian A, Tucker M, Tucker K, Merriman T, Guilford P.

Hum Mutat. 2002 May;19(5):518-25.

PubMed [citation]
PMID:
11968084

Hereditary diffuse gastric cancer: association with lobular breast cancer.

Schrader KA, Masciari S, Boyd N, Wiyrick S, Kaurah P, Senz J, Burke W, Lynch HT, Garber JE, Huntsman DG.

Fam Cancer. 2008;7(1):73-82. Review.

PubMed [citation]
PMID:
18046629
PMCID:
PMC2253650
See all PubMed Citations (4)

Details of each submission

From Ambry Genetics, SCV000665081.6

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

The c.1565+1G>C intronic pathogenic mutation results from a G to C substitution one nucleotide after coding exon 10 of the CDH1 gene. This alteration was identified in a proband with diffuse gastric cancer who had a family history of gastric cancer and lobular breast cancer (Hansford S et al. JAMA Oncol. 2015 Apr;1(1):23-32). In addition, two different splicing mutations at the same position, c.1565+1G>T and c.1565+1G>A, have previously been detected in families affected with hereditary diffuse gastric cancer (Humar B et al. Hum Mutat. 2002;19(5):518-25; Schrader KA et al. Fam Cancer. 2008;7:73-82; Huynh JM et al. Mol Genet Genomic Med. 2016 Mar;4(2):232-6). In addition to the clinical data presented in the literature, alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. RNA studies have demonstrated that this alteration results in abnormal splicing in the set of samples tested (Ambry internal data). As such, this alteration is classified as a disease-causing mutation.

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

Last Updated: Sep 29, 2024