Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001324379 | SCV001515331 | likely pathogenic | Aicardi-Goutieres syndrome 5 | 2022-10-03 | criteria provided, single submitter | clinical testing | In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. 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 disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 1024222). This variant has been observed in individual(s) with clinical features of Aicardi-Goutieres syndrome (Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change affects codon 536 of the SAMHD1 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the SAMHD1 protein. This variant also falls at the last nucleotide of exon 14, which is part of the consensus splice site for this exon. |