NM_015726.4(DCAF8):c.949C>T (p.Arg317Cys) AND Giant axonal neuropathy 2

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Mar 11, 2014
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

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:: RCV000119848.10

Allele description [Variation Report for NM_015726.4(DCAF8):c.949C>T (p.Arg317Cys)]

NM_015726.4(DCAF8):c.949C>T (p.Arg317Cys)

Gene:

DCAF8:DDB1 and CUL4 associated factor 8 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1q23.2

Genomic location:

Preferred name:

NM_015726.4(DCAF8):c.949C>T (p.Arg317Cys)

HGVS:

NC_000001.11:g.160237145G>A
NG_034154.1:g.30416C>T
NM_015726.4:c.949C>TMANE SELECT
NP_056541.2:p.Arg317Cys
NC_000001.10:g.160206935G>A
NR_028103.2:n.1482C>T
NR_028104.2:n.1408C>T
Q5TAQ9:p.Arg317Cys

Protein change:

R317C; ARG317CYS

Links:

UniProtKB: Q5TAQ9#VAR_071265; OMIM: 615820.0001; dbSNP: rs587777425

NCBI 1000 Genomes Browser:

rs587777425

Molecular consequence:

NM_015726.4:c.949C>T - missense variant - [Sequence Ontology: SO:0001583]
NR_028103.2:n.1482C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_028104.2:n.1408C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Giant axonal neuropathy 2
Synonyms:: Giant axonal neuropathy 2, autosomal dominant
Identifiers:: MONDO: MONDO:0012411; MedGen: C1864695; Orphanet: 401964; OMIM: 610100

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000154774	OMIM	no assertion criteria provided	Pathogenic (Mar 11, 2014)	germline	literature only	PubMed (2) [See all records that cite these PMIDs] 3859241, 24500646

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000154774

OMIM

no assertion criteria provided

Pathogenic
(Mar 11, 2014)

germline

literature only

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	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

Hereditary motor sensory neuropathy type II with neurofilament accumulation: new finding or new disorder?

Vogel P, Gabriel M, Goebel HH, Dyck PJ.

Ann Neurol. 1985 May;17(5):455-61.

PubMed [citation]

PMID:: 3859241

Ubiquitin ligase defect by DCAF8 mutation causes HMSN2 with giant axons.

Klein CJ, Wu Y, Vogel P, Goebel HH, Bönnemann C, Zukosky K, Botuyan MV, Duan X, Middha S, Atkinson EJ, Mer G, Dyck PJ.

Neurology. 2014 Mar 11;82(10):873-8. doi: 10.1212/WNL.0000000000000206. Epub 2014 Feb 5.

PubMed [citation]

PMID:: 24500646
PMCID:: PMC3959756

Details of each submission

From OMIM, SCV000154774.1

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

Description

In affected members of a German family with autosomal dominant giant axonal neuropathy-2 (GAN2; 610100), originally reported by Vogel et al. (1985), Klein et al. (2014) identified a heterozygous mutation in the DCAF8 gene, resulting in an arg317-to-cys (R317C) substitution at a highly conserved residue in the third WD repeat. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. It was not present in the dbSNP (build 135), 1000 Genomes Project, or Exome Variant Server databases, or in 1,536 controls of European ancestry. In vitro functional expression assays in HEK293 cells showed that the R317C mutant protein decreased DCAF8 binding to DDB1 (600045), indicating a negative impact on recruitment of the E3 ubiquitin ligase complex. Klein et al. (2014) postulated that the mutation caused a defect in E3 ubiquitin ligase-mediated neurofilament degradation.

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

Last Updated: Nov 3, 2024

ClinVar

Relating variation to medicine