ClinVar Miner

Submissions for variant NM_006397.2(RNASEH2A):c.206dup (p.Thr70fs) (rs549586181)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV000779252 SCV000915816 uncertain significance Aicardi Goutieres syndrome 4 2019-01-02 criteria provided, single submitter clinical testing The RNASEH2A c.206dupA (p.Thr70AspfsTer50) variant results in a frameshift, and is predicted to result in premature termination of the protein. This variant has been reported in two studies and is found in one seven year old child with Aicardi-Goutieres syndrome in a homozygous state and in a family with a congenital infection-like syndrome characterized by abnormal neurological signs in a heterozygous state; no additional details are provided in the second study (Crow et al. 2015; Rice et al. 2017). Control data are not available for this variant, but it is reported at a frequency of 0.002269 in the African population of the 1000 Genomes Project. Based on the limited evidence, the p.Thr70AspfsTer50 variant is classified as a variant of unknown significance but suspicious for pathogenicity for Aicardi-Goutieres syndrome. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Invitae RCV000779252 SCV000963271 pathogenic Aicardi Goutieres syndrome 4 2018-12-28 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Thr70Aspfs*50) in the RNASEH2A gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs549586181, ExAC 0.2%). This variant has been observed in an individual affected with Aicardi-Goutieres syndrome (PMID: 24183309). Loss-of-function variants in RNASEH2A are known to be pathogenic (PMID: 21454563, 25274781). For these reasons, this variant has been classified as Pathogenic.

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