NM_001139.2(ALOX12B):c.1562A>G (p.Tyr521Cys) AND Congenital ichthyosiform erythroderma

Clinical significance:Pathogenic (Last evaluated: Jun 14, 2016)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000341391.1

Allele description

NM_001139.2(ALOX12B):c.1562A>G (p.Tyr521Cys)

Gene:
ALOX12B:arachidonate 12-lipoxygenase, 12R type [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
17p13.1
Genomic location:
Preferred name:
NM_001139.2(ALOX12B):c.1562A>G (p.Tyr521Cys)
HGVS:
  • NC_000017.11:g.8075687T>C
  • NG_007099.1:g.17017A>G
  • NM_001139.2:c.1562A>G
  • NP_001130.1:p.Tyr521Cys
  • NC_000017.10:g.7979005T>C
  • O75342:p.Tyr521Cys
Protein change:
Y521C; TYR521CYS
Links:
UniProtKB: O75342#VAR_069556; OMIM: 603741.0012; dbSNP: rs199766569
NCBI 1000 Genomes Browser:
rs199766569
Allele Frequency:
0.00027(C)
Molecular consequence:
  • NM_001139.2:c.1562A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Congenital ichthyosiform erythroderma
Synonyms:
Congenital ichthyosis; Ichthyosis, congenital
Identifiers:
MedGen: CN006510; Human Phenotype Ontology: HP:0007431

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000407398Illumina Clinical Services Laboratory,Illuminacriteria provided, single submitter
Pathogenic
(Jun 14, 2016)
germlineclinical testing

PubMed (5)
[See all records that cite these PMIDs]

ICSL_Variant_Classification_20161018.pdf

Citation Link

Summary from all submissions

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

Citations

PubMed

Mutation spectrum and functional analysis of epidermis-type lipoxygenases in patients with autosomal recessive congenital ichthyosis.

Eckl KM, Krieg P, Küster W, Traupe H, André F, Wittstruck N, Fürstenberger G, Hennies HC.

Hum Mutat. 2005 Oct;26(4):351-61.

PubMed [citation]
PMID:
16116617

Molecular analysis of 250 patients with autosomal recessive congenital ichthyosis: evidence for mutation hotspots in ALOXE3 and allelic heterogeneity in ALOX12B.

Eckl KM, de Juanes S, Kurtenbach J, Nätebus M, Lugassy J, Oji V, Traupe H, Preil ML, Martínez F, Smolle J, Harel A, Krieg P, Sprecher E, Hennies HC.

J Invest Dermatol. 2009 Jun;129(6):1421-8. doi: 10.1038/jid.2008.409. Epub 2009 Jan 8.

PubMed [citation]
PMID:
19131948
See all PubMed Citations (5)

Details of each submission

From Illumina Clinical Services Laboratory,Illumina, SCV000407398.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

The c.1562A>G (p.Tyr521Cys) variant has been reported in at least six studies in which is reported in a total of ten patients with congenital ichthyosis, including four in a homozygous state, five in a compound heterozygous state, and one in a heterozygous state where a second variant was not identified (Eckl et al. 2005; Eckl et al. 2009; Vahlquist et al. 2010; Suresh et al. 2015). The p.Tyr521Cys variant was absent from 390 controls but is reported at a frequency of 0.00060 in the European (Finnish) population of the Exome Aggregation Consortium. Functional analysis in HEK-293 cells revealed that the variant resulted in protein expression levels comparable to wild type, but complete loss of enzymatic activity (Eckl et al. 2005; Eckl et al. 2009). Based on the evidence, the p.Tyr521Cys variant is classified as pathogenic for congenital ichthyosis.

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

Last Updated: Apr 3, 2017