ClinVar Miner

Submissions for variant NM_007254.4(PNKP):c.1295_1298+6del (rs587784366)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000188473 SCV000700789 likely pathogenic not provided 2016-06-28 criteria provided, single submitter clinical testing
GeneDx RCV000188473 SCV000242087 pathogenic not provided 2013-09-19 criteria provided, single submitter clinical testing The c.1295_1298+6delCCAGGTAGCG mutation in the PNKP gene results in the deletion of ten nucleotides at the exon 14/intron 14 boundary, thereby destroying the canonical splice donor site in intron 14. It is predicted to cause abnormal gene splicing, either leading to an abnormal message that is subject to nonsense-mediated mRNA decay or to an abnormal protein product if the message is used for protein translation. Although this mutation has not been previously reported to our knowledge, it is considered a disease-causing mutation.The variant is found in CHILD-EPI,EPILEPSY panel(s).
Genetic Services Laboratory, University of Chicago RCV000147346 SCV000194721 pathogenic Early infantile epileptic encephalopathy 10 2014-06-05 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000825541 SCV000966857 likely pathogenic Ataxia-oculomotor apraxia type 1 2016-12-23 criteria provided, single submitter clinical testing The c.1295_1298+6del (NM_007254.3 c.1295_1298+6delCCAGGTAGCG) variant in PNKP ha s not been reported in the literature. It has been identified in 2/8264 of South Asian chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadi nstitute.org; dbSNP rs587784366). This variant is predicted to alter splicing or cause a frameshift at this position. This alteration is then predicted to lead to a truncated or absent protein. Biallelic loss of function of the PNKP gene h as been associated with ataxia with oculomotor apraxia. In summary, although add itional studies are required to fully establish a null effect on the protein, th e c.1295_1298+6delCCAGGTAGCG variant in PNKP is likely pathogenic for ataxia wit h oculomotor apraxia in an autosomal recessive manner based upon its predicted f unctional impact.

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