7-81950426-C-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.
The NM_000722.4(CACNA2D1):c.3242G>T(p.Trp1081Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000363 in 1,461,214 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.000036 ( 0 hom. )
Consequence
CACNA2D1
NM_000722.4 missense
NM_000722.4 missense
Scores
11
6
Clinical Significance
Conservation
PhyloP100: 6.12
Genes affected
CACNA2D1 (HGNC:1399): (calcium voltage-gated channel auxiliary subunit alpha2delta 1) The preproprotein encoded by this gene is cleaved into multiple chains that comprise the alpha-2 and delta subunits of the voltage-dependent calcium channel complex. Calcium channels mediate the influx of calcium ions into the cell upon membrane polarization. Mutations in this gene can cause cardiac deficiencies, including Brugada syndrome and short QT syndrome. Alternate splicing results in multiple transcript variants, some of which may lack the delta subunit portion. [provided by RefSeq, Nov 2014]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CACNA2D1 | NM_000722.4 | c.3242G>T | p.Trp1081Leu | missense_variant | 39/39 | ENST00000356860.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CACNA2D1 | ENST00000356860.8 | c.3242G>T | p.Trp1081Leu | missense_variant | 39/39 | 1 | NM_000722.4 | ||
CACNA2D1 | ENST00000443883.2 | c.3278G>T | p.Trp1093Leu | missense_variant | 39/39 | 5 | P1 | ||
CACNA2D1 | ENST00000705962.1 | c.3122G>T | p.Trp1041Leu | missense_variant | 38/38 | ||||
CACNA2D1 | ENST00000705961.1 | c.3011G>T | p.Trp1004Leu | missense_variant | 37/37 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD3 exomes AF: 0.00000797 AC: 2AN: 250884Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135564
GnomAD3 exomes
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250884
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GnomAD4 exome AF: 0.0000363 AC: 53AN: 1461214Hom.: 0 Cov.: 30 AF XY: 0.0000316 AC XY: 23AN XY: 726910
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
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Cov.:
32
TwinsUK
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Brugada syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 27, 2023 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. This variant has not been reported in the literature in individuals affected with CACNA2D1-related conditions. This variant is present in population databases (rs773980191, gnomAD 0.002%). This sequence change replaces tryptophan, which is neutral and slightly polar, with leucine, which is neutral and non-polar, at codon 1081 of the CACNA2D1 protein (p.Trp1081Leu). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
Cadd
Uncertain
Dann
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Uncertain
D;D
Sift4G
Uncertain
D;D
Polyphen
P;.
Vest4
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at