NM_004360.5(CDH1):c.1334A>C (p.Glu445Ala) AND Hereditary cancer-predisposing syndrome

Clinical significance:Conflicting interpretations of pathogenicity, Likely benign(1);Uncertain significance(1) (Last evaluated: Dec 21, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, conflicting interpretations

Based on:
3 submissions [Details]
Record status:
current
Accession:
RCV000115839.11

Allele description [Variation Report for NM_004360.5(CDH1):c.1334A>C (p.Glu445Ala)]

NM_004360.5(CDH1):c.1334A>C (p.Glu445Ala)

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.1334A>C (p.Glu445Ala)
Other names:
p.E445A:GAG>GCG
HGVS:
  • NC_000016.10:g.68815528A>C
  • NG_008021.1:g.83237A>C
  • NM_001317184.2:c.1151A>C
  • NM_001317185.2:c.-215A>C
  • NM_001317186.2:c.-486A>C
  • NM_004360.5:c.1334A>CMANE SELECT
  • NP_001304113.1:p.Glu384Ala
  • NP_004351.1:p.Glu445Ala
  • LRG_301t1:c.1334A>C
  • LRG_301:g.83237A>C
  • NC_000016.9:g.68849431A>C
  • NM_004360.3:c.1334A>C
  • NM_004360.4:c.1334A>C
  • p.E445A
Protein change:
E384A
Links:
dbSNP: rs374398608
NCBI 1000 Genomes Browser:
rs374398608
Molecular consequence:
  • NM_001317185.2:c.-215A>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001317186.2:c.-486A>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001317184.2:c.1151A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_004360.5:c.1334A>C - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

Condition(s)

Name:
Hereditary cancer-predisposing syndrome
Synonyms:
Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0015356; MedGen: C0027672

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000186103Ambry Geneticscriteria provided, single submitter
Likely benign
(Sep 28, 2020)
germlineclinical testing

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

Citation Link,

SCV000684353Color Health, Inccriteria provided, single submitter
Uncertain significance
(Dec 21, 2020)
germlineclinical testing

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

SCV000787975True Health Diagnosticsno assertion criteria providedUncertain significance
(Sep 11, 2017)
germlineclinical testing

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown1not providednot provided1not providedclinical testing

Citations

PubMed

Frequent germline deleterious mutations in DNA repair genes in familial prostate cancer cases are associated with advanced disease.

Leongamornlert D, Saunders E, Dadaev T, Tymrakiewicz M, Goh C, Jugurnauth-Little S, Kozarewa I, Fenwick K, Assiotis I, Barrowdale D, Govindasami K, Guy M, Sawyer E, Wilkinson R; UKGPCS Collaborators., Antoniou AC, Eeles R, Kote-Jarai Z.

Br J Cancer. 2014 Mar 18;110(6):1663-72. doi: 10.1038/bjc.2014.30. Epub 2014 Feb 20.

PubMed [citation]
PMID:
24556621
PMCID:
PMC3960610

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

Details of each submission

From Ambry Genetics, SCV000186103.6

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (1)

Description

Other strong data supporting benign classification

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknown1not providednot provided1not providednot providednot provided

From Color Health, Inc, SCV000684353.4

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

Description

This missense variant replaces glutamic acid with alanine at codon 445 of the CDH1 protein. To our knowledge, functional studies have not been reported for this variant. This variant has been observed in an individual with personal or family history of prostate cancer (PMID: 24556621). This variant has been identified in 4/282852 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

From True Health Diagnostics, SCV000787975.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Jun 19, 2021

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