rs200260399
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_201596.3(CACNB2):c.1892A>G(p.Lys631Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000248 in 1,613,674 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 (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K631E) has been classified as Uncertain significance.
Frequency
Consequence
NM_201596.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CACNB2 | NM_201596.3 | c.1892A>G | p.Lys631Arg | missense_variant | 14/14 | ENST00000324631.13 | |
CACNB2 | NM_201590.3 | c.1730A>G | p.Lys577Arg | missense_variant | 13/13 | ENST00000377329.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CACNB2 | ENST00000324631.13 | c.1892A>G | p.Lys631Arg | missense_variant | 14/14 | 1 | NM_201596.3 | ||
CACNB2 | ENST00000377329.10 | c.1730A>G | p.Lys577Arg | missense_variant | 13/13 | 1 | NM_201590.3 | ||
ENST00000425669.1 | n.377-334T>C | intron_variant, non_coding_transcript_variant | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 152070Hom.: 0 Cov.: 30
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461604Hom.: 0 Cov.: 35 AF XY: 0.00000413 AC XY: 3AN XY: 727102
GnomAD4 genome ? AF: 0.00000658 AC: 1AN: 152070Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 74264
ClinVar
Submissions by phenotype
Brugada syndrome 4 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 14, 2022 | 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 191437). This variant has not been reported in the literature in individuals affected with CACNB2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces lysine, which is basic and polar, with arginine, which is basic and polar, at codon 577 of the CACNB2 protein (p.Lys577Arg). - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | research | Biesecker Lab/Clinical Genomics Section, National Institutes of Health | Jun 24, 2013 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at