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:: RCV000804448.2

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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000944359	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 30, 2018)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000944359

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 30, 2018)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical 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 Labcorp Genetics (formerly Invitae), Labcorp, SCV000944359.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical 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.

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

Last Updated: Sep 29, 2024

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