Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002150250 | SCV002418509 | likely benign | RASopathy | 2024-01-05 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV003235678 | SCV003933750 | benign | not specified | 2023-05-01 | criteria provided, single submitter | clinical testing | Variant summary: BRAF c.608+18C>T alters a non-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 9.6e-05 in 250454 control chromosomes (gnomAD). The observed variant frequency is approximately 20 fold of the estimated maximal expected allele frequency for a pathogenic variant in BRAF causing Cardiofaciocutaneous Syndrome phenotype (4.7e-06), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.608+18C>T in individuals affected with Cardiofaciocutaneous Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. One ClinVar submitter has assessed the variant since 2014: the variant was classified as likely benign. Based on the evidence outlined above, the variant was classified as benign. |