rs373826838
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_201596.3(CACNB2):āc.1747G>Cā(p.Ala583Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000062 in 1,613,828 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A583V) has been classified as Uncertain significance.
Frequency
Consequence
NM_201596.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CACNB2 | NM_201596.3 | c.1747G>C | p.Ala583Pro | missense_variant | 14/14 | ENST00000324631.13 | |
CACNB2 | NM_201590.3 | c.1585G>C | p.Ala529Pro | missense_variant | 13/13 | ENST00000377329.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CACNB2 | ENST00000324631.13 | c.1747G>C | p.Ala583Pro | missense_variant | 14/14 | 1 | NM_201596.3 | ||
CACNB2 | ENST00000377329.10 | c.1585G>C | p.Ala529Pro | missense_variant | 13/13 | 1 | NM_201590.3 | ||
ENST00000425669.1 | n.377-189C>G | intron_variant, non_coding_transcript_variant | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000132 AC: 2AN: 151978Hom.: 0 Cov.: 30
GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251286Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135824
GnomAD4 exome AF: 0.00000547 AC: 8AN: 1461850Hom.: 0 Cov.: 35 AF XY: 0.00000275 AC XY: 2AN XY: 727226
GnomAD4 genome ? AF: 0.0000132 AC: 2AN: 151978Hom.: 0 Cov.: 30 AF XY: 0.0000135 AC XY: 1AN XY: 74220
ClinVar
Submissions by phenotype
Brugada syndrome 4 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 02, 2021 | This sequence change replaces alanine with proline at codon 529 of the CACNB2 protein (p.Ala529Pro). The alanine residue is weakly conserved and there is a small physicochemical difference between alanine and proline. This variant is present in population databases (rs373826838, ExAC 0.01%). This variant has not been reported in the literature in individuals affected with CACNB2-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 14, 2022 | The p.A529P variant (also known as c.1585G>C), located in coding exon 13 of the CACNB2 gene, results from a G to C substitution at nucleotide position 1585. The alanine at codon 529 is replaced by proline, an amino acid with highly similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at