ClinVar Miner

Submissions for variant NM_021222.3(PRUNE1):c.383G>A (p.Arg128Gln) (rs767769359)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000437046 SCV000525098 likely pathogenic not provided 2016-11-08 criteria provided, single submitter clinical testing The R128Q variant in the PRUNE gene has been reported previously in the heterozygous state with another PRUNE nonsense variant in two siblings with severe developmental delay and regression, seizures, and microcephaly marked by cerebral and cerebellar volume loss (Karaca et al., 2015). The R128Q variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The R128Q variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position where amino acids with similar properties to Arginine are tolerated across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. The R128Q variant is a strong candidate for a pathogenic variant, however the possibility it may be a rare benign variant cannot be excluded.
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine RCV000454286 SCV000537908 likely pathogenic Abnormality of brain morphology criteria provided, single submitter research There are 3 more families with similar phenotype
Baylor Genetics RCV000490541 SCV001523167 pathogenic Neurodevelopmental disorder with microcephaly, hypotonia, and variable brain anomalies 2020-07-28 criteria provided, single submitter clinical testing This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868].
OMIM RCV000490541 SCV000577903 pathogenic Neurodevelopmental disorder with microcephaly, hypotonia, and variable brain anomalies 2017-09-19 no assertion criteria provided literature only

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