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NM_015378.4(VPS13D):c.3569G>A (p.Gly1190Asp) AND Autosomal recessive cerebellar ataxia-saccadic intrusion syndrome

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Sep 14, 2018
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:
RCV000680228.2

Allele description [Variation Report for NM_015378.4(VPS13D):c.3569G>A (p.Gly1190Asp)]

NM_015378.4(VPS13D):c.3569G>A (p.Gly1190Asp)

Gene:
VPS13D:vacuolar protein sorting 13 homolog D [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
1p36.22
Genomic location:
Preferred name:
NM_015378.4(VPS13D):c.3569G>A (p.Gly1190Asp)
HGVS:
  • NC_000001.11:g.12277157G>A
  • NG_056877.1:g.52119G>A
  • NM_015378.4:c.3569G>AMANE SELECT
  • NM_018156.4:c.3569G>A
  • NP_056193.2:p.Gly1190Asp
  • NP_060626.2:p.Gly1190Asp
  • LRG_1213t1:c.3569G>A
  • LRG_1213:g.52119G>A
  • LRG_1213p1:p.Gly1190Asp
  • NC_000001.10:g.12337214G>A
  • NM_015378.2:c.3569G>A
Protein change:
G1190D; GLY1190ASP
Links:
OMIM: 608877.0001; dbSNP: rs1557680919
NCBI 1000 Genomes Browser:
rs1557680919
Molecular consequence:
  • NM_015378.4:c.3569G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_018156.4:c.3569G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Autosomal recessive cerebellar ataxia-saccadic intrusion syndrome
Synonyms:
SPINOCEREBELLAR ATAXIA 24; Spinocerebellar ataxia autosomal recessive 4; Spinocerebellar ataxia 24 (formerly)
Identifiers:
MONDO: MONDO:0011811; MedGen: C1846492; Orphanet: 95434; OMIM: 607317

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000807682OMIM
no assertion criteria provided
Pathogenic
(Sep 14, 2018)
germlineliterature only

PubMed (2)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

A form of inherited cerebellar ataxia with saccadic intrusions, increased saccadic speed, sensory neuropathy, and myoclonus.

Swartz BE, Burmeister M, Somers JT, Rottach KG, Bespalova IN, Leigh RJ.

Ann N Y Acad Sci. 2002 Apr;956:441-4. No abstract available.

PubMed [citation]
PMID:
11960835

Mutations in VPS13D lead to a new recessive ataxia with spasticity and mitochondrial defects.

Seong E, Insolera R, Dulovic M, Kamsteeg EJ, Trinh J, Brüggemann N, Sandford E, Li S, Ozel AB, Li JZ, Jewett T, Kievit AJA, Münchau A, Shakkottai V, Klein C, Collins CA, Lohmann K, van de Warrenburg BP, Burmeister M.

Ann Neurol. 2018 Jun;83(6):1075-1088. doi: 10.1002/ana.25220. Epub 2018 Jun 30.

PubMed [citation]
PMID:
29604224
PMCID:
PMC6105379

Details of each submission

From OMIM, SCV000807682.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (2)

Description

In affected members of a family (UM1) with autosomal recessive spinocerebellar ataxia-4 (SCAR4; 607317), originally been reported by Swartz et al. (2002), Seong et al. (2018) identified compound heterozygous mutations in the VPS13D gene: a c.3569G-A transition (c.3569G-A, NM_015378), resulting in a gly1190-to-asp (G1190D) substitution at a conserved residue and a c.3316C-T transition, resulting in a gln1106-to-ter (Q1106X; 608877.0002) substitution. The mutations, which were found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. Neither mutation was found in the gnomAD database. Analysis of patient cells indicated that the nonsense mutation resulted in nonsense-mediated mRNA decay. Patient fibroblasts showed abnormal mitochondrial morphology, with high amounts of perinuclear spherical or donut-shaped objects and decreased mitochondrial branching compared to controls.

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

Last Updated: Mar 5, 2024