Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Women's Health and Genetics/Laboratory Corporation of America, |
RCV001174936 | SCV001338387 | uncertain significance | not specified | 2020-02-24 | criteria provided, single submitter | clinical testing | Variant summary: HRAS c.450+17C>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 1e-05 in 392786 control chromosomes, exclusively found within the African or African-American subpopulation at a frequency of 6.9e-05 (i.e. 4/ 58158 alleles) in the gnomAD database (gnomAD v2.1 exomes dataset and gnomAD v3 genomes dataset). The available data on variant occurrences (i.e. allele count) in the general population are insufficient to allow clear conclusion about variant significance, however the variant still might represent a rare benign polymorphism. To our knowledge, no occurrence of c.450+17C>T 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 VUS-possibly benign. |
Labcorp Genetics |
RCV002559679 | SCV003030514 | likely benign | Costello syndrome | 2023-03-27 | criteria provided, single submitter | clinical testing |