Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Women's Health and Genetics/Laboratory Corporation of America, |
RCV001193861 | SCV001363011 | benign | not specified | 2019-10-21 | criteria provided, single submitter | clinical testing | Variant summary: BRAF c.2128-27_2128-18del10 deletes ten nucleotides located close to a canonical splice site and therefore could affect mRNA splicing. 5/5 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 0.01 in 143638 control chromosomes, predominantly at a frequency of 0.035 within the African or African-American subpopulation in the gnomAD database, including 33 homozygotes. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 14000 fold of the estimated maximal expected allele frequency for a pathogenic variant in BRAF causing Noonan Syndrome and Related Conditions phenotype (2.5e-06), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African or African-American origin. To our knowledge, no occurrence of c.2128-27_2128-18del10 in individuals affected with Noonan Syndrome and Related Conditions and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as benign. |
Gene |
RCV001534186 | SCV001751090 | likely benign | not provided | 2019-08-11 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV002069240 | SCV002443507 | likely benign | RASopathy | 2024-01-31 | criteria provided, single submitter | clinical testing | |
Ce |
RCV001534186 | SCV004161128 | likely benign | not provided | 2024-11-01 | criteria provided, single submitter | clinical testing | BRAF: BS2 |