rs111772206
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_000722.4(CACNA2D1):c.1735-6T>G variant causes a splice region, splice polypyrimidine tract, intron change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: not found (cov: 32)
Consequence
CACNA2D1
NM_000722.4 splice_region, splice_polypyrimidine_tract, intron
NM_000722.4 splice_region, splice_polypyrimidine_tract, intron
Scores
2
Splicing: ADA: 0.9774
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 4.19
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 3 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF. No scorers claiming Uncertain. Scorers claiming Benign: max_spliceai.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CACNA2D1 | NM_000722.4 | c.1735-6T>G | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000356860.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CACNA2D1 | ENST00000356860.8 | c.1735-6T>G | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_000722.4 | ||||
CACNA2D1 | ENST00000443883.2 | c.1792-6T>G | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 5 | P1 | ||||
CACNA2D1 | ENST00000705961.1 | c.1502-6T>G | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ||||||
CACNA2D1 | ENST00000705962.1 | c.1636-6T>G | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 20
GnomAD4 exome
Cov.:
20
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
Bravo
AF:
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Pathogenic
dbscSNV1_RF
Pathogenic
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at