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

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.83

Links

CACNA1A (HGNC:1388):

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
CACNA1A	NM_001127222.2 linkuse as main transcript	c.6203G>C	p.Arg2068Pro	missense_variant	43/47	ENST00000360228.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CACNA1A	ENST00000360228.11 linkuse as main transcript	c.6203G>C	p.Arg2068Pro	missense_variant	43/47	1	NM_001127222.2		O00555-8

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152220

Hom.:

Cov.:

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:

AN:

1461494

Hom.:

AF XY:

0.00

AC XY:

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

BayesDel_noAF

Pathogenic

0.14

Cadd

Uncertain

Dann

Uncertain

0.99

Eigen

Benign

0.017

Eigen_PC

Benign

0.0032

FATHMM_MKL

Uncertain

0.88

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

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

MutationTaster

Benign

0.95

D;D;D

PrimateAI

Uncertain

0.55

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

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Links

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over