rs373932682
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The ENST00000352115.10(CACNB2):c.725G>A(p.Arg242Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000477 in 1,612,690 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/15 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. R242W) has been classified as Uncertain significance.
Frequency
Consequence
ENST00000352115.10 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_201590.3 | c.642+665G>A | intron_variant | ENST00000377329.10 | |||
CACNB2 | NM_201596.3 | c.804+665G>A | intron_variant | ENST00000324631.13 | |||
LOC124902386 | XR_007062076.1 | n.3880C>T | non_coding_transcript_exon_variant | 2/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CACNB2 | ENST00000324631.13 | c.804+665G>A | intron_variant | 1 | NM_201596.3 | ||||
CACNB2 | ENST00000377329.10 | c.642+665G>A | intron_variant | 1 | NM_201590.3 | ||||
ENST00000425669.1 | n.483-1374C>T | intron_variant, non_coding_transcript_variant | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000526 AC: 8AN: 152134Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000518 AC: 13AN: 251088Hom.: 0 AF XY: 0.0000589 AC XY: 8AN XY: 135728
GnomAD4 exome AF: 0.0000472 AC: 69AN: 1460556Hom.: 0 Cov.: 30 AF XY: 0.0000413 AC XY: 30AN XY: 726678
GnomAD4 genome ? AF: 0.0000526 AC: 8AN: 152134Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74306
ClinVar
Submissions by phenotype
Brugada syndrome 4 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Aug 24, 2021 | - - |
Brugada syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | research | CSER _CC_NCGL, University of Washington | Oct 01, 2016 | Found in patient having exome sequencing for an unrelated indication. No known history of Brugada syndrome. This interpretation considers GERP score and allele frequency data, in addition to published reports of the variant in the literature, available at the time of review. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Feb 01, 2023 | Has not been previously published as pathogenic or benign to our knowledge; Identified independently and in conjunction with additional variants in individuals referred for cardiac genetic testing at GeneDx; segregation data is limited or absent at this time; In silico analysis supports that this missense variant does not alter protein structure/function; p.(R242Q) is located in an alternative transcript of the CACNB2 gene in which no definitive pathogenic variants have been reported in association with cardiogenetic disorders (HGMD); Variants in candidate genes are classified as variants of uncertain significance in accordance with ACMG guidelines (Richards et al., 2015) - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at