Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Clin |
RCV001172271 | SCV001335309 | likely benign | RASopathy | 2020-01-31 | reviewed by expert panel | curation | The c.*7T>C variant in the 3' UTR of BRAF is classified as likely benign because it occurs in a noncoding region, computational splice analyses do not predict an impact on splicing, and Alamut indicates that this nucleotide is not highly conserved (BP4, BP7). It has been identified in 0.0008791% (1/113754) of non-Finnish European chromosomes in gnomAD v2. RASopathy-specific ACMG/AMP Criteria applied (PMID:29493581): BP4, BP7. |
| Laboratory for Molecular Medicine, |
RCV000150196 | SCV000197118 | likely benign | not specified | 2010-08-06 | criteria provided, single submitter | clinical testing | The 2301+7T>C variant in BRAF occurs in the 3' UTR. This variant has not been pr eviously reported in the literature or been identified in our laboratory. This v ariant is not located in a region of high nucleotide conservation; however, this type of variant has not been previously reported as pathogenic in an individual with a Noonan spectrum disorder. The 3'UTR contains regulatory elements essenti al for the regulation and transport of the mRNA transcript, and variants in this region could result in dysregulation or disruption of these functions. While it is likely that this variant is benign, we cannot rule out that it may contribut e to the clinical features observed in this individual. |
| Illumina Laboratory Services, |
RCV000301466 | SCV000466942 | uncertain significance | LEOPARD syndrome 3 | 2018-01-13 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. |
| Illumina Laboratory Services, |
RCV000337738 | SCV000466943 | uncertain significance | Noonan syndrome 7 | 2018-01-13 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000150196 | SCV004020965 | uncertain significance | not specified | 2023-06-10 | criteria provided, single submitter | clinical testing |