10-18140752-AT-A
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_201596.3(CACNB2):c.17delT(p.Met6fs) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000139 in 1,442,932 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
CACNB2
NM_201596.3 frameshift
NM_201596.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.108
Genes affected
CACNB2 (HGNC:1402): (calcium voltage-gated channel auxiliary subunit beta 2) This gene encodes a subunit of a voltage-dependent calcium channel protein that is a member of the voltage-gated calcium channel superfamily. The gene product was originally identified as an antigen target in Lambert-Eaton myasthenic syndrome, an autoimmune disorder. Mutations in this gene are associated with Brugada syndrome. Alternatively spliced variants encoding different isoforms have been described. [provided by RefSeq, Feb 2013]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CACNB2 | NM_201596.3 | c.17delT | p.Met6fs | frameshift_variant | 1/14 | ENST00000324631.13 | NP_963890.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CACNB2 | ENST00000324631.13 | c.17delT | p.Met6fs | frameshift_variant | 1/14 | 1 | NM_201596.3 | ENSP00000320025.8 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD3 exomes AF: 0.00000476 AC: 1AN: 210142Hom.: 0 AF XY: 0.00000872 AC XY: 1AN XY: 114676
GnomAD3 exomes
AF:
AC:
1
AN:
210142
Hom.:
AF XY:
AC XY:
1
AN XY:
114676
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: 0.00000139 AC: 2AN: 1442932Hom.: 0 Cov.: 32 AF XY: 0.00000279 AC XY: 2AN XY: 715838
GnomAD4 exome
AF:
AC:
2
AN:
1442932
Hom.:
Cov.:
32
AF XY:
AC XY:
2
AN XY:
715838
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 Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jul 10, 2014 | The c.17delT variant has not been published as a mutation or reported as a benign polymorphism to our knowledge. This variant occurs in an alternate transcript of the CACNB2 gene. No definitive loss of function mutations in the CACNB2 gene have been reported in association with familial arrhythmia suggesting that haploinsufficiency may not be a disease mechanism for CACNB2-associated arrhythmia. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. - |
CACNB2-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jul 06, 2023 | The CACNB2 c.17delT variant is predicted to result in a frameshift and premature protein termination (p.Met6Serfs*21). To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0011% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/10-18429681-AT-A). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
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