ClinVar Miner

Submissions for variant NM_032193.4(RNASEH2C):c.205C>T (rs78635798)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000414153 SCV000344847 likely pathogenic not provided 2016-08-15 criteria provided, single submitter clinical testing
GeneDx RCV000414153 SCV000490775 pathogenic not provided 2018-01-04 criteria provided, single submitter clinical testing The R69W pathogenic variant in the RNASEH2C gene has been reported previously in the homozygous state in multiple individuals from South Asia or the Middle East with Aicardi-Goutieres syndrome, including two siblings with significantly different presentations, suggesting clinical variability (Rice et al., 2007; Ramantani et al., 2010; Vogt et al., 2013; Al-Shamsi et al., 2016; Hebbar et al., 2018). The R69W variant is observed in 21/30,782 (0.068%) alleles from individuals of South Asian background in large population cohorts (Lek et al., 2016). The R69W variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. Functional studies demonstrate that R69W is associated with decreased enzyme activity and reduced thermal stability of RNaseH2 (Chon et al., 2009; Reijns et al., 2011). We interpret R69W as a pathogenic variant.
SIB Swiss Institute of Bioinformatics RCV000001322 SCV000803569 likely pathogenic Aicardi Goutieres syndrome 3 2018-05-31 criteria provided, single submitter curation This variant is interpreted as a Likely Pathogenic, for Aicardi-Goutieres syndrome 3, in Autosomal Recessive manner. The following ACMG Tag(s) were applied: PP3 => Multiple lines of computational evidence support a deleterious effect on the gene or gene product. PP1 => Cosegregation with disease in multiple affected family members in a gene definitively known to cause the disease (PMID:23322642) (PMID:16845400). PM2 => Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium. PS4-Moderate => Recurrent mutation observed in multiple patients. (PMID:17846997,16845400,20131292,23322642,29150899).
Fulgent Genetics,Fulgent Genetics RCV000001322 SCV000893907 pathogenic Aicardi Goutieres syndrome 3 2018-10-31 criteria provided, single submitter clinical testing
Kasturba Medical College, Manipal University RCV000001322 SCV001478362 likely pathogenic Aicardi Goutieres syndrome 3 2020-02-17 criteria provided, single submitter clinical testing
OMIM RCV000001322 SCV000021472 pathogenic Aicardi Goutieres syndrome 3 2013-02-01 no assertion criteria provided literature only

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