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rs769040794

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2_SupportingPP2

The NM_001127222(CACNA1A):c.6203G>C(p.Arg2068Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152220 control chromosomes in the gnomAD Genomes database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R2068Q) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 34)

Consequence

CACNA1A
NM_001127222 missense

Scores

3
6
5

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.83

Links

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
?
Very rare variant; Number of alleles below threshold, gnomad allele frequency = 0.00000657 (1/152220) while in subpopulation NFE AF= 0.0000147 (1/68044). AF 95% confidence interval is 0. There are 0 homozygotes in gnomad. There are 0 alleles in male gnomad subpopulation. Median coverage is 34. This position pass quality control queck.
PP2
?
Missense variant where missense usually causes diseases, CACNA1A

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CACNA1ANM_001127222.2 linkuse as main transcriptc.6203G>C p.Arg2068Pro missense_variant 43/47 ENST00000360228.11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CACNA1AENST00000360228.11 linkuse as main transcriptc.6203G>C p.Arg2068Pro missense_variant 43/471 NM_001127222.2 O00555-8

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152220
Hom.:
0
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461494
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
727066
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.0000383
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.00e-7
Gnomad4 OTH exome
AF:
0.00
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.38
BayesDel_addAF
Pathogenic
0.26
D
BayesDel_noAF
Pathogenic
0.14
Cadd
Uncertain
24
Dann
Uncertain
0.99
Eigen
Benign
0.017
Eigen_PC
Benign
0.0032
FATHMM_MKL
Uncertain
0.88
D
LIST_S2
Uncertain
0.96
D;D;D;D;D;D;D;D;D;D;.;D;D;D;D;D;D;D
M_CAP
Pathogenic
0.31
D
MetaRNN
Uncertain
0.70
D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM
Benign
-0.44
T
MutationTaster
Benign
0.95
D;D;D
PrimateAI
Uncertain
0.55
T
Sift4G
Benign
0.097
T;T;.;.;.;T;.;.;.;.;.;.;.;.;.;.;.;.
Vest4
0.66
MutPred
0.21
.;.;Gain of glycosylation at S2065 (P = 0.1008);Gain of glycosylation at S2065 (P = 0.1008);Gain of glycosylation at S2065 (P = 0.1008);.;.;Gain of glycosylation at S2065 (P = 0.1008);.;.;.;Gain of glycosylation at S2065 (P = 0.1008);Gain of glycosylation at S2065 (P = 0.1008);.;Gain of glycosylation at S2065 (P = 0.1008);.;.;.;
MVP
0.93
MPC
0.85
ClinPred
0.99
D
GERP RS
3.4
Varity_R
0.72
gMVP
0.58

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs769040794; hg19: chr19-13323017;