rs1229502
Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1
The NM_000722.4(CACNA2D1):c.3114C>T(p.Pro1038=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.295 in 1,606,426 control chromosomes in the GnomAD database, including 72,019 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.25 ( 5505 hom., cov: 32)
Exomes 𝑓: 0.30 ( 66514 hom. )
Consequence
CACNA2D1
NM_000722.4 synonymous
NM_000722.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.215
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 Benign. Variant got -19 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.4).
BP6
?
Variant 7-81959320-G-A is Benign according to our data. Variant chr7-81959320-G-A is described in ClinVar as [Benign]. Clinvar id is 256767.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-81959320-G-A is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=0.215 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.306 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CACNA2D1 | NM_000722.4 | c.3114C>T | p.Pro1038= | synonymous_variant | 38/39 | ENST00000356860.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CACNA2D1 | ENST00000356860.8 | c.3114C>T | p.Pro1038= | synonymous_variant | 38/39 | 1 | NM_000722.4 | ||
CACNA2D1 | ENST00000443883.2 | c.3150C>T | p.Pro1050= | synonymous_variant | 38/39 | 5 | P1 | ||
CACNA2D1 | ENST00000705962.1 | c.2994C>T | p.Pro998= | synonymous_variant | 37/38 | ||||
CACNA2D1 | ENST00000705961.1 | c.2883C>T | p.Pro961= | synonymous_variant | 36/37 |
Frequencies
GnomAD3 genomes ? AF: 0.255 AC: 38638AN: 151658Hom.: 5504 Cov.: 32
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GnomAD3 exomes AF: 0.291 AC: 72862AN: 250768Hom.: 11027 AF XY: 0.292 AC XY: 39629AN XY: 135524
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GnomAD4 exome AF: 0.299 AC: 435612AN: 1454650Hom.: 66514 Cov.: 31 AF XY: 0.300 AC XY: 217288AN XY: 724108
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GnomAD4 genome ? AF: 0.255 AC: 38636AN: 151776Hom.: 5505 Cov.: 32 AF XY: 0.256 AC XY: 18954AN XY: 74154
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ClinVar
Significance: Benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 28, 2016 | 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. - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Apr 20, 2017 | - - |
Brugada syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Cardiovascular phenotype Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 19, 2015 | This alteration is classified as 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
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at