rs141327265
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Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 2P and 17B. PM2BP4_StrongBP6_Very_StrongBP7BS1
The NM_006030.4(CACNA2D2):āc.669T>Cā(p.Asn223=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000238 in 1,584,188 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 (ā ā ).
Frequency
Genomes: š 0.00030 ( 0 hom., cov: 32)
Exomes š: 0.00023 ( 0 hom. )
Consequence
CACNA2D2
NM_006030.4 synonymous
NM_006030.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.260
Genes affected
CACNA2D2 (HGNC:1400): (calcium voltage-gated channel auxiliary subunit alpha2delta 2) Calcium channels mediate the entry of calcium ions into the cell upon membrane polarization. This gene encodes the alpha-2/delta subunit of the voltage-dependent calcium channel complex. The complex consists of the main channel-forming subunit alpha-1, and auxiliary subunits alpha-2/delta, beta, and gamma. The auxiliary subunits function in the assembly and membrane localization of the complex, and modulate calcium currents and channel activation/inactivation kinetics. The subunit encoded by this gene undergoes post-translational cleavage to yield the extracellular alpha2 peptide and a membrane-anchored delta polypeptide. This subunit is a receptor for the antiepileptic drug, gabapentin. Mutations in this gene are associated with early infantile epileptic encephalopathy. Single nucleotide polymorphisms in this gene are correlated with increased sensitivity to opioid drugs. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Mar 2014]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -15 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.49).
BP6
Variant 3-50381110-A-G is Benign according to our data. Variant chr3-50381110-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 416547.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=0.26 with no splicing effect.
BS1
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.000297 (45/151450) while in subpopulation AMR AF= 0.00059 (9/15260). AF 95% confidence interval is 0.000307. There are 0 homozygotes in gnomad4. There are 25 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CACNA2D2 | NM_006030.4 | c.669T>C | p.Asn223= | synonymous_variant | 7/38 | ENST00000424201.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CACNA2D2 | ENST00000424201.7 | c.669T>C | p.Asn223= | synonymous_variant | 7/38 | 1 | NM_006030.4 | P4 |
Frequencies
GnomAD3 genomes AF: 0.000291 AC: 44AN: 151332Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000458 AC: 115AN: 251146Hom.: 0 AF XY: 0.000472 AC XY: 64AN XY: 135726
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GnomAD4 exome AF: 0.000232 AC: 332AN: 1432738Hom.: 0 Cov.: 33 AF XY: 0.000223 AC XY: 159AN XY: 712922
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GnomAD4 genome AF: 0.000297 AC: 45AN: 151450Hom.: 0 Cov.: 32 AF XY: 0.000338 AC XY: 25AN XY: 74048
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Apr 01, 2023 | CACNA2D2: BP4, BP7 - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Feb 11, 2020 | - - |
Early infantile epileptic encephalopathy with suppression bursts Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 10, 2024 | - - |
Computational scores
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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