rs147728344
Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_000722.4(CACNA2D1):c.2682C>T(p.Pro894=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000465 in 1,612,508 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000049 ( 0 hom. )
Consequence
CACNA2D1
NM_000722.4 synonymous
NM_000722.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.31
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -17 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.91).
BP6
?
Variant 7-81964252-G-A is Benign according to our data. Variant chr7-81964252-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 512548.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-2.31 with no splicing effect.
BS2
?
High AC in GnomAdExome at 12 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CACNA2D1 | NM_000722.4 | c.2682C>T | p.Pro894= | synonymous_variant | 33/39 | ENST00000356860.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CACNA2D1 | ENST00000356860.8 | c.2682C>T | p.Pro894= | synonymous_variant | 33/39 | 1 | NM_000722.4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000198 AC: 3AN: 151734Hom.: 0 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
3
AN:
151734
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0000479 AC: 12AN: 250558Hom.: 0 AF XY: 0.0000517 AC XY: 7AN XY: 135398
GnomAD3 exomes
AF:
AC:
12
AN:
250558
Hom.:
AF XY:
AC XY:
7
AN XY:
135398
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000493 AC: 72AN: 1460774Hom.: 0 Cov.: 32 AF XY: 0.0000454 AC XY: 33AN XY: 726708
GnomAD4 exome
AF:
AC:
72
AN:
1460774
Hom.:
Cov.:
32
AF XY:
AC XY:
33
AN XY:
726708
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.0000198 AC: 3AN: 151734Hom.: 0 Cov.: 32 AF XY: 0.0000270 AC XY: 2AN XY: 74078
GnomAD4 genome
?
AF:
AC:
3
AN:
151734
Hom.:
Cov.:
32
AF XY:
AC XY:
2
AN XY:
74078
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 17, 2017 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Brugada syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jul 08, 2021 | - - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 10, 2018 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
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