Submissions for variant NM_201596.3(CACNB2):c.671-18T>C

gnomAD frequency: 0.00011  dbSNP: rs551760338

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002128392	SCV002454829	benign	Brugada syndrome 4	2024-12-02	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV004782890	SCV005395575	benign	not specified	2024-09-09	criteria provided, single submitter	clinical testing	Variant summary: CACNB2 c.509-18T>C alters a conserved nucleotide located at a position not widely known to affect splicing. Consensus agreement among computation 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 0.00059 in 251180 control chromosomes. The observed variant frequency is approximately 59 fold of the estimated maximal expected allele frequency for a pathogenic variant in CACNB2 causing Arrhythmia phenotype (1e-05). To our knowledge, no occurrence of c.509-18T>C in individuals affected with Arrhythmia and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 1636476). Based on the evidence outlined above, the variant was classified as benign.