rs753131879
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Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7
The NM_006030.4(CACNA2D2):c.2154C>T(p.Phe718=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000045 in 888,486 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 0.0000071 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000040 ( 0 hom. )
Consequence
CACNA2D2
NM_006030.4 synonymous
NM_006030.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 2.08
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 Likely_benign. Variant got -5 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.5).
BP6
?
Variant 3-50367892-G-A is Benign according to our data. Variant chr3-50367892-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 461308.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=2.09 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CACNA2D2 | NM_006030.4 | c.2154C>T | p.Phe718= | synonymous_variant | 25/38 | ENST00000424201.7 | |
LOC101928965 | NR_183064.1 | n.1066G>A | non_coding_transcript_exon_variant | 2/2 | |||
LOC127898564 | NR_183066.1 | n.966G>A | non_coding_transcript_exon_variant | 5/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CACNA2D2 | ENST00000424201.7 | c.2154C>T | p.Phe718= | synonymous_variant | 25/38 | 1 | NM_006030.4 | P4 | |
ENST00000607121.5 | n.699G>A | non_coding_transcript_exon_variant | 3/3 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00000710 AC: 1AN: 140896Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000162 AC: 4AN: 246212Hom.: 0 AF XY: 0.0000150 AC XY: 2AN XY: 133448
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GnomAD4 exome AF: 0.00000401 AC: 3AN: 747590Hom.: 0 Cov.: 32 AF XY: 0.00000259 AC XY: 1AN XY: 386028
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GnomAD4 genome ? AF: 0.00000710 AC: 1AN: 140896Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 68244
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Early infantile epileptic encephalopathy with suppression bursts Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 23, 2020 | - - |
Computational scores
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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