U.S. flag

An official website of the United States government

NM_004360.5(CDH1):c.866C>T (p.Ala289Val) AND Hereditary diffuse gastric adenocarcinoma

Germline classification:
Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:
Dec 29, 2023
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:
RCV000196783.21

Allele description [Variation Report for NM_004360.5(CDH1):c.866C>T (p.Ala289Val)]

NM_004360.5(CDH1):c.866C>T (p.Ala289Val)

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.866C>T (p.Ala289Val)
Other names:
NM_004360.5(CDH1):c.866C>T; p.Ala289Val
HGVS:
  • NC_000016.10:g.68811717C>T
  • NG_008021.1:g.79426C>T
  • NM_001317184.2:c.866C>T
  • NM_001317185.2:c.-750C>T
  • NM_001317186.2:c.-954C>T
  • NM_004360.4:c.866C>T
  • NM_004360.5:c.866C>TMANE SELECT
  • NP_001304113.1:p.Ala289Val
  • NP_004351.1:p.Ala289Val
  • LRG_301t1:c.866C>T
  • LRG_301:g.79426C>T
  • NC_000016.9:g.68845620C>T
  • NM_004360.3:c.866C>T
Protein change:
A289V
Links:
dbSNP: rs780399325
NCBI 1000 Genomes Browser:
rs780399325
Molecular consequence:
  • NM_001317185.2:c.-750C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001317186.2:c.-954C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001317184.2:c.866C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_004360.5:c.866C>T - 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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000254833Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Dec 29, 2023) 		germlineclinical testing

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

SCV003926698European 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))		Likely benign
(Aug 1, 2022) 		germlineclinical testing

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

Help

Summary from all submissions

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

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
See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000254833.10

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

Description

This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 289 of the CDH1 protein (p.Ala289Val). This variant is present in population databases (rs780399325, gnomAD 0.01%). This missense change has been observed in individual(s) with breast cancer (PMID: 30287823). ClinVar contains an entry for this variant (Variation ID: 216597). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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

From European Reference Network on Genetic Tumour Risk Syndromes (ERN-GENTURIS), i3s - Instituto de Investigação e Inovação em Saúde, University of Porto - ERN GENTURIS, SCV003926698.1

#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"

PubMed [ID: 36436516]

Description

BS2 (PMID: 30311375)

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

Last Updated: Oct 13, 2024