NM_001127222.2(CACNA1A):c.4997G>A (p.Arg1666Gln) AND Spastic ataxia

Clinical significance:Uncertain significance (Last evaluated: Nov 1, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000855537.1

Allele description [Variation Report for NM_001127222.2(CACNA1A):c.4997G>A (p.Arg1666Gln)]

NM_001127222.2(CACNA1A):c.4997G>A (p.Arg1666Gln)

Gene:
CACNA1A:calcium voltage-gated channel subunit alpha1 A [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
19p13.13
Genomic location:
Preferred name:
NM_001127222.2(CACNA1A):c.4997G>A (p.Arg1666Gln)
HGVS:
  • NC_000019.10:g.13235684C>T
  • NG_011569.1:g.275777G>A
  • NM_000068.4:c.5015G>A
  • NM_001127221.1:c.5000G>A
  • NM_001127222.2:c.4997G>AMANE SELECT
  • NM_001174080.2:c.5006G>A
  • NM_023035.3:c.5015G>A
  • NP_000059.3:p.Arg1672Gln
  • NP_001120693.1:p.Arg1667Gln
  • NP_001120694.1:p.Arg1666Gln
  • NP_001167551.1:p.Arg1669Gln
  • NP_075461.2:p.Arg1672Gln
  • LRG_7t1:c.5000G>A
  • LRG_7:g.275777G>A
  • LRG_7p1:p.Arg1667Gln
  • NC_000019.9:g.13346498C>T
  • NM_000068.2:c.5000G>A
  • NM_000068.3:c.5015G>A
Protein change:
R1666Q
Links:
dbSNP: rs1568447650
NCBI 1000 Genomes Browser:
rs1568447650
Molecular consequence:
  • NM_000068.4:c.5015G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001127221.1:c.5000G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001127222.2:c.4997G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001174080.2:c.5006G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_023035.3:c.5015G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Spastic ataxia
Identifiers:
MONDO: MONDO:0017845; MedGen: C1849156; OMIM: PS108600; Human Phenotype Ontology: HP:0002497

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000998566Care4Rare-SOLVE, CHEO - Care4Rarecriteria provided, single submitter
Uncertain significance
(Nov 1, 2019)
germlineresearch

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyes1not providednot providednot providednot providedresearch

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 Care4Rare-SOLVE, CHEO - Care4Rare, SCV000998566.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
11not providednot providedresearch PubMed (1)

Description

This missense variant in exon 32 has not been seen in healthy control populations (EVS, 1000Genomes, ExAC, gnomAD) and is predicted to impact protein structure/and or function by in silico analysis programs(SIFT, PolyPhen-2, CADD). While no one has been reported with the same nucleic acid base change, one other individual was reported with this same amino acid change and a similar spastic presentation (Coutelier et al. 2018. PMID: 29482223). Two other individuals had a similar amino acid change at this location and also presented with hemiplegic migraines and spasticity. Segregation of this variant in unaffected relatives was not available.

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

Last Updated: Apr 12, 2021

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