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NM_004360.5(CDH1):c.2644G>A (p.Asp882Asn) AND Hereditary diffuse gastric adenocarcinoma

Germline classification:
Conflicting interpretations of pathogenicity (3 submissions)
Last evaluated:
Jan 21, 2024
Review status:
criteria provided, conflicting classifications
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:
RCV000232913.12

Allele description

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]
Observations:
2

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

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000288478Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Likely benign
(Jan 21, 2024)
germlineclinical testing

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

SCV001424797Division of Medical Genetics, University of Washington - CSER_CHARM
criteria provided, single submitter

(ACMG Guidelines, 2015)
Uncertain significance
(Aug 9, 2019)
germlineclinical testing

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

SCV003926975European Reference Network on Genetic Tumour Risk Syndromes (ERN-GENTURIS), i3s - Instituto de Investigação e Inovação em Saúde, University of Porto - ERN GENTURIS
criteria provided, single submitter

(Lee et al. (Hum Mutat. 2018))
Uncertain significance
(Aug 1, 2022)
germlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenonot provided2not providednot providednot providedclinical testing
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

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

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
See all PubMed Citations (4)

Details of each submission

From Invitae, SCV000288478.10

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

From Division of Medical Genetics, University of Washington - CSER_CHARM, SCV001424797.1

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

Description

To our knowledge, this sequence variant has not been previously reported in the literature. The p.Asp882Asn variant has an overall allele frequency of 0.00005305 in the Broad Institute gnomAD Browser (https://gnomad.broadinstitute.org/). In silico analyses indicate that this variant may have a deleterious effect due to its relative conservation and predicted impact on the final protein product. It is unknown at this time whether this variant increases cancer risk; therefore, we consider it to be a variant of uncertain significance (VUS).

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

From European Reference Network on Genetic Tumour Risk Syndromes (ERN-GENTURIS), i3s - Instituto de Investigação e Inovação em Saúde, University of Porto - ERN GENTURIS, SCV003926975.1

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

Description

"2 families not fulfilling 2020 HDGC criteria-2 Familial history of breast cancer"

Description

Not applicable criteria (PMID: 30311375)

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenonot providednot providednot providednot providednot provided2not provided

Last Updated: May 26, 2024