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NM_018052.5(VAC14):c.2005G>T (p.Val669Leu) AND Striatonigral degeneration, childhood-onset

Germline classification:
Uncertain significance (1 submission)
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
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:
RCV000984879.2

Allele description [Variation Report for NM_018052.5(VAC14):c.2005G>T (p.Val669Leu)]

NM_018052.5(VAC14):c.2005G>T (p.Val669Leu)

Gene:
VAC14:VAC14 component of PIKFYVE complex [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
16q22.1
Genomic location:
Preferred name:
NM_018052.5(VAC14):c.2005G>T (p.Val669Leu)
HGVS:
  • NC_000016.10:g.70695574C>A
  • NG_054902.1:g.110596G>T
  • NM_001351157.2:c.1303G>T
  • NM_018052.5:c.2005G>TMANE SELECT
  • NP_001338086.1:p.Val435Leu
  • NP_060522.3:p.Val669Leu
  • NC_000016.9:g.70729477C>A
  • NM_018052.3:c.2005G>T
Protein change:
V435L
Links:
dbSNP: rs1363536856
NCBI 1000 Genomes Browser:
rs1363536856
Molecular consequence:
  • NM_001351157.2:c.1303G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_018052.5:c.2005G>T - missense variant - [Sequence Ontology: SO:0001583]
Functional consequence:
variation affecting protein [Variation Ontology: 0002]
Observations:
1

Condition(s)

Name:
Striatonigral degeneration, childhood-onset (SNDC)
Synonyms:
LENK-PLOSKI SYNDROME
Identifiers:
MONDO: MONDO:0014889; MedGen: C4310743; OMIM: 617054

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000925663Genome Medicine, Institute for Basic Research in Developmental Disabilities
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain significanceinheritedclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
mixed Syrian and non-Syrian Jewish ancestryinheritedyes21not providednot providednot providedclinical testing

Citations

PubMed

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 Genome Medicine, Institute for Basic Research in Developmental Disabilities, SCV000925663.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1mixed Syrian and non-Syrian Jewish ancestry2not providednot providedclinical testing PubMed (1)

Description

Whole-exome sequencing was used to identify the genetic etiology of a rapidly progressing neurological disease present in two of six siblings with early childhood onset of severe progressive spastic paraparesis and learning disabilities. A homozygous mutation (c.2005G>T, p.V669L) was found in VAC14, and the clinical phenotype is consistent with the recently described VAC-related striatonigral degeneration, childhood-onset syndrome (SNDC) (MIM#617054). However, the phenotype includes a distinct clinical presentation of retinitis pigmentosa (RP), which has not previously been reported in association with VAC14 mutations. Brain magnetic resonance imaging (MRI) revealed abnormal magnetic susceptibility in the globus pallidus, which can be seen in neurodegeneration with brain iron accumulation (NBIA). RP is a group of inherited retinal diseases with phenotypic/genetic heterogeneity, and the pathophysiologic basis of RP is not completely understood but is thought to be due to a primary retinal photoreceptor cell degenerative process. Most cases of RP are seen in isolation (non-syndromic); this is a report of RP in two siblings with VAC14-associated syndrome, and it is suggested that a connection between RP and VAC14-associated syndrome should be explored in future studies.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1inheritedyesnot providednot providednot provided2not provided1not provided

Last Updated: Nov 18, 2024