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NM_004360.5(CDH1):c.2644G>A (p.Asp882Asn) AND Hereditary cancer-predisposing syndrome

Germline classification:
Uncertain significance (2 submissions)
Last evaluated:
Apr 3, 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:
RCV000115860.16

Allele description [Variation Report for NM_004360.5(CDH1):c.2644G>A (p.Asp882Asn)]

NM_004360.5(CDH1):c.2644G>A (p.Asp882Asn)

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.2644G>A (p.Asp882Asn)
Other names:
p.D882N:GAC>AAC
HGVS:
  • NC_000016.10:g.68833494G>A
  • NG_008021.1:g.101203G>A
  • NM_001317184.2:c.2461G>A
  • NM_001317185.2:c.1096G>A
  • NM_001317186.2:c.679G>A
  • NM_004360.5:c.2644G>AMANE SELECT
  • NP_001304113.1:p.Asp821Asn
  • NP_001304114.1:p.Asp366Asn
  • NP_001304115.1:p.Asp227Asn
  • NP_004351.1:p.Asp882Asn
  • LRG_301t1:c.2644G>A
  • LRG_301:g.101203G>A
  • NC_000016.9:g.68867397G>A
  • NM_004360.3:c.2644G>A
  • NM_004360.4:c.2644G>A
  • p.D882N
Protein change:
D227N
Links:
dbSNP: rs200104963
NCBI 1000 Genomes Browser:
rs200104963
Molecular consequence:
  • NM_001317184.2:c.2461G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001317185.2:c.1096G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001317186.2:c.679G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_004360.5:c.2644G>A - missense variant - [Sequence Ontology: SO:0001583]

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

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000184064Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)
Uncertain significance
(Aug 3, 2022)
germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Citation Link,

SCV000689523Color Diagnostics, LLC DBA Color Health
criteria provided, single submitter

(ACMG Guidelines, 2015)
Uncertain significance
(Apr 3, 2023)
germlineclinical testing

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

Summary from all submissions

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

Citations

PubMed

Germline pathogenic variants of 11 breast cancer genes in 7,051 Japanese patients and 11,241 controls.

Momozawa Y, Iwasaki Y, Parsons MT, Kamatani Y, Takahashi A, Tamura C, Katagiri T, Yoshida T, Nakamura S, Sugano K, Miki Y, Hirata M, Matsuda K, Spurdle AB, Kubo M.

Nat Commun. 2018 Oct 4;9(1):4083. doi: 10.1038/s41467-018-06581-8.

PubMed [citation]
PMID:
30287823
PMCID:
PMC6172276

Multigene panel testing beyond BRCA1/2 in breast/ovarian cancer Spanish families and clinical actionability of findings.

Bonache S, Esteban I, Moles-Fernández A, Tenés A, Duran-Lozano L, Montalban G, Bach V, Carrasco E, Gadea N, López-Fernández A, Torres-Esquius S, Mancuso F, Caratú G, Vivancos A, Tuset N, Balmaña J, Gutiérrez-Enríquez S, Diez O.

J Cancer Res Clin Oncol. 2018 Dec;144(12):2495-2513. doi: 10.1007/s00432-018-2763-9. Epub 2018 Oct 10.

PubMed [citation]
PMID:
30306255
See all PubMed Citations (4)

Details of each submission

From Ambry Genetics, SCV000184064.8

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

The p.D882N variant (also known as c.2644G>A), located in coding exon 16 of the CDH1 gene, results from a G to A substitution at nucleotide position 2644. The aspartic acid at codon 882 is replaced by asparagine, an amino acid with highly similar properties. This alteration has been reported in an individual with ductal carcinoma in situ diagnosed at age 29 with a family history of diffuse gastric cancer diagnosed at age 52 in a maternal cousin (Bonache S et al. J. Cancer Res. Clin. Oncol., 2018 Dec;144:2495-2513). This alteration has also been reported in breast cancer cases, as well as in controls (Momozawa Y et al. Nat Commun, 2018 10;9:4083; Dorling et al. N Engl J Med. 2021 02;384:428-439). This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited 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, SCV000689523.5

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

Description

This missense variant replaces aspartic acid with asparagine at codon 882 of the CDH1 protein. To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individuals affected with breast cancer, but also in unaffected individuals in the literature (PMID: 30287823, 30306255, 33471991). This variant has been identified in 15/282744 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

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

Last Updated: Jun 23, 2024