Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001913470 | SCV002183157 | uncertain significance | Aicardi-Goutieres syndrome 3 | 2024-10-23 | criteria provided, single submitter | clinical testing | This sequence change affects a donor splice site in intron 2 of the RNASEH2C gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), however the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in RNASEH2C cause disease. This variant is present in population databases (no rsID available, gnomAD 0.002%). Disruption of this splice site has been observed in individual(s) with RNASEH2C-related condition (PMID: 25500883). ClinVar contains an entry for this variant (Variation ID: 1409111). Algorithms developed to predict the effect of variants on gene product structure and function are not available or were not evaluated for this variant. Experimental studies have shown that disruption of this splice site affects RNASEH2C function (PMID: 25500883). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus 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. |