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

This record was updated by the submitter. Please see the current version.

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:

Condition(s)

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

Recent activity

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LOC126926744 [Bombus affinis]
LOC126926744 [Bombus affinis]
Gene ID:126926744

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000288478	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely benign (Jan 21, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001424797	Division of Medical Genetics, University of Washington - CSER_CHARM	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Aug 9, 2019)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV003926975	European 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)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 30311375, 36436516

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000288478

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely benign
(Jan 21, 2024)

germline

clinical testing

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

SCV001424797

Division of Medical Genetics, University of Washington - CSER_CHARM

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Aug 9, 2019)

germline

clinical testing

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

SCV003926975

European 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)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	no	not provided	2	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical 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

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

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

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical 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).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	no	not provided	not provided	not provided		not provided	not provided	not provided	not 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

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

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

PubMed [ID: 36436516]

Description

Not applicable criteria (PMID: 30311375)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	no	not provided	not provided	not provided		not provided	not provided	2	not provided

Last Updated: May 26, 2024

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