Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV002438068 | SCV002751846 | uncertain significance | Cardiovascular phenotype | 2021-11-05 | criteria provided, single submitter | clinical testing | The c.290+3G>T intronic variant results from a G to T substitution 3 nucleotides after coding exon 2 in the HRAS gene. This nucleotide position is well conserved in available vertebrate species. In silico splice site analysis predicts that this alteration may result in the creation or strengthening of a novel splice donor site. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Labcorp Genetics |
RCV003102855 | SCV003261225 | uncertain significance | Costello syndrome | 2023-08-16 | criteria provided, single submitter | clinical testing | This sequence change falls in intron 3 of the HRAS gene. It does not directly change the encoded amino acid sequence of the HRAS protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs771562113, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with HRAS-related conditions. ClinVar contains an entry for this variant (Variation ID: 1797443). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |