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NM_004360.5(CDH1):c.387+2T>A AND Hereditary cancer-predisposing syndrome

Germline classification:
Uncertain significance (2 submissions)
Last evaluated:
Jun 26, 2023
Review status:
2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts
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:
RCV001021328.7

Allele description [Variation Report for NM_004360.5(CDH1):c.387+2T>A]

NM_004360.5(CDH1):c.387+2T>A

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.387+2T>A
HGVS:
  • NC_000016.10:g.68801895T>A
  • NG_008021.1:g.69604T>A
  • NM_001317184.2:c.387+2T>A
  • NM_001317185.2:c.-1229+2T>A
  • NM_001317186.2:c.-1433+2T>A
  • NM_004360.5:c.387+2T>AMANE SELECT
  • LRG_301t1:c.387+2T>A
  • LRG_301:g.69604T>A
  • NC_000016.9:g.68835798T>A
  • NM_004360.3:c.387+2T>A
  • NM_004360.4:c.387+2T>A
Links:
dbSNP: rs903144020
NCBI 1000 Genomes Browser:
rs903144020
Molecular consequence:
  • NM_001317184.2:c.387+2T>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001317185.2:c.-1229+2T>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001317186.2:c.-1433+2T>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_004360.5:c.387+2T>A - 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
SCV001182930Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Uncertain significance
(Jun 26, 2023) 		germlineclinical testing

Citation Link,

SCV001341371Color Diagnostics, LLC DBA Color Health
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain significance
(Apr 2, 2019) 		germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

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

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From Ambry Genetics, SCV001182930.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The c.387+2T>A intronic variant results from a T to A substitution two nucleotides after coding exon 3 in the CDH1 gene. This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice donor site. RNA studies have demonstrated that this alteration results in multiple in-frame splicing events of unknown functional significance (Ambry internal data). Another alteration at this same splice donor site, c.387+1G>A, is also predicted by in silico models to disrupt splicing. Internal RNA studies demonstrated that the c.387+1G>A variant similarly results in multiple in-frame splicing events of unknown functional significance (Ambry internal data). In addition, the c.387+2T>A alteration has been identified in individuals that do not have a personal or family history suggestive of hereditary diffuse gastric cancer (Ambry internal data). Since supporting evidence is conflicting at this time, the clinical significance of this alteration remains unclear.

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

From Color Diagnostics, LLC DBA Color Health, SCV001341371.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024