ClinVar Miner

Submissions for variant NM_007055.4(POLR3A):c.1740dup (p.Val581fs) (rs781745727)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000292592 SCV000329967 pathogenic not provided 2016-06-21 criteria provided, single submitter clinical testing The c.1740dupA pathogenic variant in the POLR3A gene has been reported previously in association with hypomyelinating leukodystrophy, in an affected individual who was heterozygous for the c.1740dupA variant and another variant. (Daoud et al., 2013). The c.1740dupA variant causes a frameshift starting with codon Valine 581, changes this amino acid to a Serine residue, and creates a premature Stop codon at position 28 of the new reading frame, denoted p.Val581SerfsX28. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.1740dupA variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. We interpret c.1740dupA as a pathogenic variant.
GeneReviews RCV001541986 SCV001760621 pathogenic Hypomyelinating leukodystrophy 7 2017-05-11 no assertion criteria provided literature only

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