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NM_004360.5(CDH1):c.387+2T>A AND Hereditary diffuse gastric adenocarcinoma

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Nov 22, 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:
RCV001063454.6

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 diffuse gastric adenocarcinoma (HDGC)
Synonyms:
Hereditary diffuse gastric cancer
Identifiers:
MONDO: MONDO:0007648; MedGen: C1708349; Orphanet: 26106; OMIM: 137215

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Assertion and evidence details

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Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001228301Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Nov 22, 2023) 		germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link

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Summary from all submissions

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

Citations

PubMed

Pathogenic and likely pathogenic variants in PALB2, CHEK2, and other known breast cancer susceptibility genes among 1054 BRCA-negative Hispanics with breast cancer.

Weitzel JN, Neuhausen SL, Adamson A, Tao S, Ricker C, Maoz A, Rosenblatt M, Nehoray B, Sand S, Steele L, Unzeitig G, Feldman N, Blanco AM, Hu D, Huntsman S, Castillo D, Haiman C, Slavin T, Ziv E.

Cancer. 2019 Aug 15;125(16):2829-2836. doi: 10.1002/cncr.32083. Epub 2019 Jun 17.

PubMed [citation]
PMID:
31206626
PMCID:
PMC7376605

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001228301.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

This sequence change affects a donor splice site in intron 3 of the CDH1 gene. RNA analysis indicates that disruption of this splice site induces altered splicing and likely results in the loss of 53 or insertion of 19 amino acid residue(s), but is expected to preserve the integrity of the reading-frame. This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individual(s) with breast cancer. However, it has not been observed in individuals with hereditary diffuse gastric cancer (PMID: 31206626; Invitae). ClinVar contains an entry for this variant (Variation ID: 824323). Studies have shown that disruption of this splice site results in the activation of a cryptic splice site in intron 3 and exon 2 (Poster G20 in http://jmd.amjpathol.org/article/S1525-1578(16)30178-7/pdf). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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

Last Updated: Sep 29, 2024