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NM_001127222.2(CACNA1A):c.4089+3G>A AND multiple conditions

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Aug 30, 2018
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:
RCV000804448.1

Allele description [Variation Report for NM_001127222.2(CACNA1A):c.4089+3G>A]

NM_001127222.2(CACNA1A):c.4089+3G>A

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.4089+3G>A
HGVS:
  • NC_000019.10:g.13262731C>T
  • NG_011569.1:g.248730G>A
  • NM_000068.4:c.4101+3G>A
  • NM_001127221.2:c.4092+3G>A
  • NM_001127222.2:c.4089+3G>AMANE SELECT
  • NM_001174080.2:c.4092+3G>A
  • NM_023035.3:c.4101+3G>A
  • LRG_7t1:c.4092+3G>A
  • LRG_7:g.248730G>A
  • NC_000019.9:g.13373545C>T
  • NM_001127221.1:c.4092+3G>A
Links:
dbSNP: rs781595676
NCBI 1000 Genomes Browser:
rs781595676
Molecular consequence:
  • NM_000068.4:c.4101+3G>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001127221.2:c.4092+3G>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001127222.2:c.4089+3G>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001174080.2:c.4092+3G>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_023035.3:c.4101+3G>A - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Name:
Episodic ataxia type 2 (EA2)
Synonyms:
Episodic ataxia with nystagmus; Nystagmus-associated episodic ataxia; Cerebellopathy, hereditary paroxysmal; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0007163; MedGen: C1720416; Orphanet: 97; OMIM: 108500
Name:
Developmental and epileptic encephalopathy, 42 (DEE42)
Synonyms:
Epileptic encephalopathy, early infantile, 42
Identifiers:
MONDO: MONDO:0014917; MedGen: C4310716; OMIM: 617106

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000944359Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Aug 30, 2018) 		germlineclinical testing

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

Help

Summary from all submissions

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

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV000944359.1

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

Description

This sequence change falls in intron 25 of the CACNA1A gene. It does not directly change the encoded amino acid sequence of the CACNA1A protein, but it affects a nucleotide within the consensus splice site of the intron. This variant is present in population databases (rs781595676, ExAC 0.08%). This variant has not been reported in the literature in individuals with CACNA1A-related disease. ClinVar contains an entry for this variant (Variation ID: 290399). Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing, but this prediction has not been confirmed by published transcriptional studies. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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

Last Updated: Aug 5, 2023