GeneBe

rs16054

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP3

The NM_001127222.2(CACNA1A):​c.6946_6975delCAGCAGCAGCAGCAGCAGCAGCAGCAGCAG​(p.Gln2316_Gln2325del) variant causes a conservative inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000349 in 1,431,740 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: 𝑓 0.0000068 ( 0 hom., cov: 0)
Exomes 𝑓: 0.0000031 ( 0 hom. )

Consequence

CACNA1A
NM_001127222.2 conservative_inframe_deletion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.785

Publications

10 publications found
Variant links:
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 2
    Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Genomics England PanelApp, Orphanet
  • undetermined early-onset epileptic encephalopathy
    Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Illumina, Orphanet
  • developmental and epileptic encephalopathy, 42
    Inheritance: AD Classification: STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
  • migraine, familial hemiplegic, 1
    Inheritance: AD Classification: STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
  • spinocerebellar ataxia type 6
    Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Ambry Genetics
  • benign paroxysmal torticollis of infancy
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • familial or sporadic hemiplegic migraine
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • Lennox-Gastaut syndrome
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

BP3
Nonframeshift variant in repetitive region in NM_001127222.2

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001127222.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
CACNA1A
NM_001127222.2
MANE Select
c.6946_6975delCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGp.Gln2316_Gln2325del
conservative_inframe_deletion
Exon 47 of 47NP_001120694.1O00555-8
CACNA1A
NM_001127221.2
MANE Plus Clinical
c.*158_*187delCAGCAGCAGCAGCAGCAGCAGCAGCAGCAG
3_prime_UTR
Exon 47 of 47NP_001120693.1O00555-3
CACNA1A
NM_023035.3
c.6964_6993delCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGp.Gln2322_Gln2331del
conservative_inframe_deletion
Exon 48 of 48NP_075461.2A0A087WW63

Ensembl Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
CACNA1A
ENST00000360228.11
TSL:1 MANE Select
c.6946_6975delCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGp.Gln2316_Gln2325del
conservative_inframe_deletion
Exon 47 of 47ENSP00000353362.5O00555-8
CACNA1A
ENST00000638029.1
TSL:5
c.6964_6993delCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGp.Gln2322_Gln2331del
conservative_inframe_deletion
Exon 48 of 48ENSP00000489829.1A0A087WW63
CACNA1A
ENST00000573710.7
TSL:5
c.6952_6981delCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGp.Gln2318_Gln2327del
conservative_inframe_deletion
Exon 47 of 47ENSP00000460092.3A0A1C7CYY9

Frequencies

GnomAD3 genomes
AF:
0.00000677
AC:
1
AN:
147802
Hom.:
0
Cov.:
0
show subpopulations
Gnomad AFR
AF:
0.0000249
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000312
AC:
4
AN:
1283938
Hom.:
0
AF XY:
0.00000475
AC XY:
3
AN XY:
631946
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
24930
American (AMR)
AF:
0.00
AC:
0
AN:
24096
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
21718
East Asian (EAS)
AF:
0.00
AC:
0
AN:
29594
South Asian (SAS)
AF:
0.00
AC:
0
AN:
65608
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
33418
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
3752
European-Non Finnish (NFE)
AF:
0.00000389
AC:
4
AN:
1027676
Other (OTH)
AF:
0.00
AC:
0
AN:
53146
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.425
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.00000677
AC:
1
AN:
147802
Hom.:
0
Cov.:
0
AF XY:
0.0000139
AC XY:
1
AN XY:
71886
show subpopulations
African (AFR)
AF:
0.0000249
AC:
1
AN:
40090
American (AMR)
AF:
0.00
AC:
0
AN:
14948
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3436
East Asian (EAS)
AF:
0.00
AC:
0
AN:
4832
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4710
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
9952
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
300
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
66616
Other (OTH)
AF:
0.00
AC:
0
AN:
2022
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.425
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
0.00
Hom.:
195

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
PhyloP100
0.79
Mutation Taster
=193/7
polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs16054; hg19: chr19-13318672; API