ClinVar Miner

Submissions for variant NM_007254.4(PNKP):c.1386+49_1387-33del (rs752902474)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV000194165 SCV000248541 pathogenic Early infantile epileptic encephalopathy 10 2013-02-08 criteria provided, single submitter clinical testing
Invitae RCV000798839 SCV000938474 pathogenic Early infantile epileptic encephalopathy 12 2018-10-01 criteria provided, single submitter clinical testing This sequence change falls in intron 15 of the PNKP gene. It does not directly change the encoded amino acid sequence of the PNKP protein. This variant is present in population databases (rs752902474, ExAC 0.03%). This variant has been observed to segregate with PNKP-related microcephaly and seizures in at least one family (PMID: 20118933). This variant is also known as g.5646_5662del and exon15fs4X  in the literature. Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Experimental studies have shown that this variant causes exon skipping and a significant decrease in cellular PNKP DNA 5' -kinase activity (PMID: 22508754, 20118933). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000194165 SCV000025299 pathogenic Early infantile epileptic encephalopathy 10 2010-03-01 no assertion criteria provided literature only

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