Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000185574 | SCV002250805 | uncertain significance | Aicardi-Goutieres syndrome 3 | 2021-07-12 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Glu60Glyfs*46) in the RNASEH2C gene. It is expected to result in an absent or disrupted protein product. However, the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in RNASEH2C cause disease. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with RNASEH2C-related conditions. ClinVar contains an entry for this variant (Variation ID: 203392). 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. |
Ambry Genetics | RCV002519569 | SCV003637515 | pathogenic | Inborn genetic diseases | 2022-09-06 | criteria provided, single submitter | clinical testing | The c.178dupG (p.E60Gfs*46) alteration, located in exon 2 (coding exon 2) of the RNASEH2C gene, consists of a duplication of G at position 178, causing a translational frameshift with a predicted alternate stop codon after 46 amino acids. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). Based on the available evidence, this alteration is classified as pathogenic. |
Division of Human Genetics, |
RCV000185574 | SCV000238474 | likely pathogenic | Aicardi-Goutieres syndrome 3 | 2015-05-26 | no assertion criteria provided | research | The RNASEH2C variant (c.178dup; p.Glu60Glyfs*46) is considered likely pathogenic because it results in the premature truncation of the transcript, which may be affected by nonsense mediated decay. Another frameshift variant has been reported downstream of this position. |
Division of Human Genetics, |
RCV000185574 | SCV000536915 | likely pathogenic | Aicardi-Goutieres syndrome 3 | 2015-05-26 | no assertion criteria provided | research |