chr19-13207431-TGCCGAGAAGGCGAGGCGCAGGCCGG-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001127222.2(CACNA1A):c.7378_7402delCCGGCCTGCGCCTCGCCTTCTCGGC(p.Pro2460fs) variant causes a frameshift change. The variant allele was found at a frequency of 0.00000073 in 1,370,606 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 31)
Exomes 𝑓: 7.3e-7 ( 0 hom. )
Consequence
CACNA1A
NM_001127222.2 frameshift
NM_001127222.2 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 3.59
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| CACNA1A | ENST00000360228.11 | c.7378_7402delCCGGCCTGCGCCTCGCCTTCTCGGC | p.Pro2460fs | frameshift_variant | 47/47 | 1 | NM_001127222.2 | ENSP00000353362.5 | ||
| CACNA1A | ENST00000638029.1 | c.7396_7420delCCGGCCTGCGCCTCGCCTTCTCGGC | p.Pro2466fs | frameshift_variant | 48/48 | 5 | ENSP00000489829.1 | |||
| CACNA1A | ENST00000573710.7 | c.7384_7408delCCGGCCTGCGCCTCGCCTTCTCGGC | p.Pro2462fs | frameshift_variant | 47/47 | 5 | ENSP00000460092.3 | |||
| CACNA1A | ENST00000635727.1 | c.7381_7405delCCGGCCTGCGCCTCGCCTTCTCGGC | p.Pro2461fs | frameshift_variant | 47/47 | 5 | ENSP00000490001.1 | |||
| CACNA1A | ENST00000637769.1 | c.7381_7405delCCGGCCTGCGCCTCGCCTTCTCGGC | p.Pro2461fs | frameshift_variant | 47/47 | 1 | ENSP00000489778.1 | |||
| CACNA1A | ENST00000636012.1 | c.7345_7369delCCGGCCTGCGCCTCGCCTTCTCGGC | p.Pro2449fs | frameshift_variant | 46/46 | 5 | ENSP00000490223.1 | |||
| CACNA1A | ENST00000637736.1 | c.7240_7264delCCGGCCTGCGCCTCGCCTTCTCGGC | p.Pro2414fs | frameshift_variant | 46/46 | 5 | ENSP00000489861.1 | |||
| CACNA1A | ENST00000636389 | c.*464_*488delCCGGCCTGCGCCTCGCCTTCTCGGC | 3_prime_UTR_variant | 47/47 | 5 | ENSP00000489992.1 | ||||
| CACNA1A | ENST00000637432 | c.*590_*614delCCGGCCTGCGCCTCGCCTTCTCGGC | 3_prime_UTR_variant | 48/48 | 5 | ENSP00000490617.1 | ||||
| CACNA1A | ENST00000635895 | c.*590_*614delCCGGCCTGCGCCTCGCCTTCTCGGC | 3_prime_UTR_variant | 47/47 | 5 | ENSP00000490323.1 | ||||
| CACNA1A | ENST00000638009 | c.*590_*614delCCGGCCTGCGCCTCGCCTTCTCGGC | 3_prime_UTR_variant | 47/47 | 1 | ENSP00000489913.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
31
GnomAD4 exome AF: 7.30e-7 AC: 1AN: 1370606Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 677616
GnomAD4 exome
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1
AN:
1370606
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0
AN XY:
677616
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GnomAD4 genome
GnomAD4 genome
Cov.:
31
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
| Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Dec 01, 2021 | - - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.