ClinVar Miner

Submissions for variant NM_024570.4(RNASEH2B):c.52T>A (p.Phe18Ile)

gnomAD frequency: 0.00001  dbSNP: rs758877268
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001327794 SCV001518883 uncertain significance Aicardi-Goutieres syndrome 2 2021-08-26 criteria provided, single submitter clinical testing This sequence change replaces phenylalanine with isoleucine at codon 18 of the RNASEH2B protein (p.Phe18Ile). The phenylalanine residue is weakly conserved and there is a small physicochemical difference between phenylalanine and isoleucine. While this variant is present in population databases (rs758877268), the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals affected with RNASEH2B-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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 RCV002546234 SCV003554166 uncertain significance Inborn genetic diseases 2020-10-30 criteria provided, single submitter clinical testing The c.52T>A (p.F18I) alteration is located in exon 1 (coding exon 1) of the RNASEH2B gene. This alteration results from a T to A substitution at nucleotide position 52, causing the phenylalanine (F) at amino acid position 18 to be replaced by an isoleucine (I). Based on data from the Genome Aggregation Database (gnomAD) database, the RNASEH2B c.52T>A alteration was observed in 0.003% (2/71988) of total alleles studied. This amino acid position is well conserved in available vertebrate species. The in silico prediction for the p.F18I alteration is inconclusive. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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