NM_004360.5(CDH1):c.1004G>A (p.Arg335Gln) AND not specified

Clinical significance:Uncertain significance (Last evaluated: Sep 6, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000855585.1

Allele description [Variation Report for NM_004360.5(CDH1):c.1004G>A (p.Arg335Gln)]

NM_004360.5(CDH1):c.1004G>A (p.Arg335Gln)

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.1004G>A (p.Arg335Gln)
Other names:
p.R335Q:CGA>CAA
HGVS:
  • NC_000016.10:g.68811855G>A
  • NG_008021.1:g.79564G>A
  • NM_001317184.2:c.1004G>A
  • NM_001317185.2:c.-612G>A
  • NM_001317186.2:c.-816G>A
  • NM_004360.5:c.1004G>AMANE SELECT
  • NP_001304113.1:p.Arg335Gln
  • NP_004351.1:p.Arg335Gln
  • LRG_301t1:c.1004G>A
  • LRG_301:g.79564G>A
  • NC_000016.9:g.68845758G>A
  • NM_004360.3:c.1004G>A
  • NM_004360.4:c.1004G>A
  • p.R335Q
Protein change:
R335Q
Links:
dbSNP: rs373364873
NCBI 1000 Genomes Browser:
rs373364873
Molecular consequence:
  • NM_001317185.2:c.-612G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001317186.2:c.-816G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001317184.2:c.1004G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_004360.5:c.1004G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000698351Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
Uncertain significance
(Sep 6, 2019)
germlineclinical testing

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

Citation Link

Summary from all submissions

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

Citations

PubMed

Relationship between E-cadherin gene mutation and p53 gene mutation, p53 accumulation, Bcl-2 expression and Ki-67 staining in diffuse-type gastric carcinoma.

Fricke E, Keller G, Becker I, Rosivatz E, Schott C, Plaschke S, Rudelius M, Hermannstädter C, Busch R, Höfler H, Becker KF, Luber B.

Int J Cancer. 2003 Mar 10;104(1):60-5.

PubMed [citation]
PMID:
12532420

Differential expression of the epithelial-mesenchymal transition regulators snail, SIP1, and twist in gastric cancer.

Rosivatz E, Becker I, Specht K, Fricke E, Luber B, Busch R, Höfler H, Becker KF.

Am J Pathol. 2002 Nov;161(5):1881-91.

PubMed [citation]
PMID:
12414534
PMCID:
PMC1850763
See all PubMed Citations (4)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000698351.2

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

Description

Variant summary: CDH1 c.1004G>A (p.Arg335Gln) results in a conservative amino acid change located in the Cadherin-like (IPR002126) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 2.4e-05 in 251236 control chromosomes, predominantly at a frequency of 5.8e-05 within the Latino subpopulation in the gnomAD database. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.1004G>A has been reported in the literature in individuals affected with gastric cancer (Rosivatz_2002, Fricke_2003), however it was not clear whether the mutation was somatic or germline in origin. In addition, the variant has been observed in an individual with colorectal cancer and no history of gastric cancer (Raskin_2017) and an individual with breast cancer (Momozawa_2018). These reports do not provide unequivocal conclusions about association of the variant with Hereditary Diffuse Gastric Cancer. Six clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar (evaluation after 2014) and cited the variant as uncertain significance. However, co-occurrence with another pathogenic variant has been reported (RAD51C c.706-2A>G), providing supporting evidence for a benign role. Based on the evidence outlined above, the variant was classified as VUS-possibly benign.

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

Last Updated: Jun 14, 2021

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