ClinVar Miner

Submissions for variant NM_201596.3(CACNB2):c.1206+3A>T

gnomAD frequency: 0.00005  dbSNP: rs200174877
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000243739 SCV000319496 likely benign Cardiovascular phenotype 2022-09-21 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Invitae RCV000547052 SCV000647059 uncertain significance Brugada syndrome 4 2022-09-03 criteria provided, single submitter clinical testing This sequence change falls in intron 10 of the CACNB2 gene. It does not directly change the encoded amino acid sequence of the CACNB2 protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs200174877, gnomAD 0.02%). This variant has been observed in individual(s) with clinical features of Brugada syndrome (PMID: 28600387). This variant is also known as c.1122+3A>T. ClinVar contains an entry for this variant (Variation ID: 180291). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. 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.
Centre for Mendelian Genomics, University Medical Centre Ljubljana RCV000547052 SCV001366451 uncertain significance Brugada syndrome 4 2019-02-15 criteria provided, single submitter clinical testing This variant was classified as: Uncertain significance. The available evidence on this variant's pathogenicity is insufficient or conflicting. The following ACMG criteria were applied in classifying this variant: BS1.
GeneDx RCV001689706 SCV001913671 uncertain significance not provided 2020-04-07 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; In-silico analysis is inconclusive as to whether the variant alters gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.; Reported in ClinVar as a variant of uncertain significance (ClinVar Variant ID# 180291; Landrum et al., 2016)
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001797638 SCV002041847 likely benign not specified 2021-11-22 criteria provided, single submitter clinical testing Variant summary: CACNB2 c.1044+3A>T alters a conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 4/4 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00011 in 251250 control chromosomes, predominantly at a frequency of 0.00022 within the Non-Finnish European subpopulation in the gnomAD database. The observed variant frequency within Non-Finnish European control individuals in the gnomAD database is approximately 70 fold of the estimated maximal expected allele frequency for a pathogenic variant in CACNB2 causing Brugada Syndrome phenotype (3.1e-06), strongly suggesting that the variant is a benign polymorphism found primarily in populations of Non-Finnish European origin. c.1044+3A>T (also known as c.1122+3A>T) has been reported in the literature in at least one individual who was a cardiac arrest survivor (Mellor_2017). This individual also had a second variant for this gene c.1558G>A and authors classified both variants as VUS. This report does not provide unequivocal conclusions about association of the variant with Brugada Syndrome. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and all laboratories classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as likely benign.
Blueprint Genetics RCV000157132 SCV000206855 uncertain significance Cardiac arrest 2014-09-18 no assertion criteria provided clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.