rs759331923
Variant names:
Your query was ambiguous. Multiple possible variants found:
- chr19-13208879-ATGGTGGTGGTGGTGGTGG-A
- chr19-13208879-ATGGTGGTGGTGGTGGTGG-ATGG
- chr19-13208879-ATGGTGGTGGTGGTGGTGG-ATGGTGG
- chr19-13208879-ATGGTGGTGGTGGTGGTGG-ATGGTGGTGG
- chr19-13208879-ATGGTGGTGGTGGTGGTGG-ATGGTGGTGGTGG
- chr19-13208879-ATGGTGGTGGTGGTGGTGG-ATGGTGGTGGTGGTGG
- chr19-13208879-ATGGTGGTGGTGGTGGTGG-ATGGTGGTGGTGGTGGTGGTGG
- chr19-13208879-ATGGTGGTGGTGGTGGTGG-ATGGTGGTGGTGGTGGTGGTGGTGG
- chr19-13208879-ATGGTGGTGGTGGTGGTGG-ATGGTGGTGGTGGTGGTGGTGGTGGTGG
Variant summary
Our verdict is Uncertain significance. The variant received 0 ACMG points: 1P and 1B. PP3BP3
The NM_023035.3(CACNA1A):c.6657_6674delCCACCACCACCACCACCA(p.His2220_His2225del) variant causes a disruptive inframe deletion change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000766 in 1,305,510 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: not found (cov: 31)
Exomes 𝑓: 7.7e-7 ( 0 hom. )
Consequence
CACNA1A
NM_023035.3 disruptive_inframe_deletion
NM_023035.3 disruptive_inframe_deletion
Scores
Not classified
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 8.26
Publications
0 publications found
Genes affected
CACNA1A (HGNC:1388): (calcium voltage-gated channel subunit alpha1 A) Voltage-dependent calcium channels mediate the entry of calcium ions into excitable cells, and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, and gene expression. Calcium channels are multisubunit complexes composed of alpha-1, beta, alpha-2/delta, and gamma subunits. The channel activity is directed by the pore-forming alpha-1 subunit, whereas, the others act as auxiliary subunits regulating this activity. The distinctive properties of the calcium channel types are related primarily to the expression of a variety of alpha-1 isoforms, alpha-1A, B, C, D, E, and S. This gene encodes the alpha-1A subunit, which is predominantly expressed in neuronal tissue. Mutations in this gene are associated with 2 neurologic disorders, familial hemiplegic migraine and episodic ataxia 2. This gene also exhibits polymorphic variation due to (CAG)n-repeats. Multiple transcript variants encoding different isoforms have been found for this gene. In one set of transcript variants, the (CAG)n-repeats occur in the 3' UTR, and are not associated with any disease. But in another set of variants, an insertion extends the coding region to include the (CAG)n-repeats which encode a polyglutamine tract. Expansion of the (CAG)n-repeats from the normal 4-18 to 21-33 in the coding region is associated with spinocerebellar ataxia 6. [provided by RefSeq, Jul 2016]
CACNA1A Gene-Disease associations (from GenCC):
- episodic ataxia type 2Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
- undetermined early-onset epileptic encephalopathyInheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, Illumina
- developmental and epileptic encephalopathy, 42Inheritance: AD Classification: STRONG, MODERATE Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
- migraine, familial hemiplegic, 1Inheritance: AD Classification: STRONG Submitted by: Ambry Genetics, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
- spinocerebellar ataxia type 6Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Orphanet
- benign paroxysmal torticollis of infancyInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- familial or sporadic hemiplegic migraineInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- Lennox-Gastaut syndromeInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
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ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 0 ACMG points.
PP3
No computational evidence supports a deleterious effect, but strongly conserved according to phyloP
BP3
Nonframeshift variant in repetitive region in NM_023035.3
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_023035.3. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| CACNA1A | NM_001127222.2 | MANE Select | c.6639_6656delCCACCACCACCACCACCA | p.His2214_His2219del | disruptive_inframe_deletion | Exon 46 of 47 | NP_001120694.1 | ||
| CACNA1A | NM_001127221.2 | MANE Plus Clinical | c.6642_6659delCCACCACCACCACCACCA | p.His2215_His2220del | disruptive_inframe_deletion | Exon 46 of 47 | NP_001120693.1 | ||
| CACNA1A | NM_023035.3 | c.6657_6674delCCACCACCACCACCACCA | p.His2220_His2225del | disruptive_inframe_deletion | Exon 47 of 48 | NP_075461.2 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| CACNA1A | ENST00000360228.11 | TSL:1 MANE Select | c.6639_6656delCCACCACCACCACCACCA | p.His2214_His2219del | disruptive_inframe_deletion | Exon 46 of 47 | ENSP00000353362.5 | ||
| CACNA1A | ENST00000638009.2 | TSL:1 MANE Plus Clinical | c.6642_6659delCCACCACCACCACCACCA | p.His2215_His2220del | disruptive_inframe_deletion | Exon 46 of 47 | ENSP00000489913.1 | ||
| CACNA1A | ENST00000638029.1 | TSL:5 | c.6657_6674delCCACCACCACCACCACCA | p.His2220_His2225del | disruptive_inframe_deletion | Exon 47 of 48 | ENSP00000489829.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
31
GnomAD4 exome AF: 7.66e-7 AC: 1AN: 1305510Hom.: 0 AF XY: 0.00000155 AC XY: 1AN XY: 645420 show subpopulations
GnomAD4 exome
AF:
AC:
1
AN:
1305510
Hom.:
AF XY:
AC XY:
1
AN XY:
645420
show subpopulations
African (AFR)
AF:
AC:
0
AN:
30304
American (AMR)
AF:
AC:
0
AN:
34384
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
23566
East Asian (EAS)
AF:
AC:
0
AN:
34222
South Asian (SAS)
AF:
AC:
0
AN:
76836
European-Finnish (FIN)
AF:
AC:
0
AN:
32500
Middle Eastern (MID)
AF:
AC:
0
AN:
4798
European-Non Finnish (NFE)
AF:
AC:
1
AN:
1014512
Other (OTH)
AF:
AC:
0
AN:
54388
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
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0
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0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
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Age
GnomAD4 genome
GnomAD4 genome
Cov.:
31
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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