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NM_007254.4(PNKP):c.1295_1298+6del AND Developmental and epileptic encephalopathy, 12

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Dec 4, 2023
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV001070856.8

Allele description [Variation Report for NM_007254.4(PNKP):c.1295_1298+6del]

NM_007254.4(PNKP):c.1295_1298+6del

Gene:
PNKP:polynucleotide kinase 3'-phosphatase [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
19q13.33
Genomic location:
Preferred name:
NM_007254.4(PNKP):c.1295_1298+6del
HGVS:
  • NC_000019.10:g.49861769_49861778del
  • NC_000019.9:g.50365023_50365032del
  • NG_027717.1:g.10791_10800del
  • NG_050666.1:g.17926_17935del
  • NM_007254.4:c.1295_1298+6delMANE SELECT
  • NC_000019.10:g.49861766_49861775delCGCTACCTGG
  • NC_000019.9:g.50365023_50365032del
  • NC_000019.9:g.50365023_50365032delCGCTACCTGG
  • NC_000019.9:g.50365026_50365035del
  • NM_007254.2:c.1295_1298+6delCCAGGTAGCG
  • NM_007254.3:c.1295_1298+6delCCAGGTAGCG
  • p.?
Links:
dbSNP: rs587784366
NCBI 1000 Genomes Browser:
rs587784366
Molecular consequence:
  • NM_007254.4:c.1295_1298+6del - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Name:
Developmental and epileptic encephalopathy, 12 (DEE12)
Synonyms:
Early infantile epileptic encephalopathy 12
Identifiers:
MONDO: MONDO:0013389; MedGen: C3150988; OMIM: 613722

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001236133Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Pathogenic
(Dec 4, 2023)
germlineclinical testing

PubMed (6)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]
PMID:
16199547
PMCID:
PMC1735933

Mutations in PNKP cause microcephaly, seizures and defects in DNA repair.

Shen J, Gilmore EC, Marshall CA, Haddadin M, Reynolds JJ, Eyaid W, Bodell A, Barry B, Gleason D, Allen K, Ganesh VS, Chang BS, Grix A, Hill RS, Topcu M, Caldecott KW, Barkovich AJ, Walsh CA.

Nat Genet. 2010 Mar;42(3):245-9. doi: 10.1038/ng.526. Epub 2010 Jan 31.

PubMed [citation]
PMID:
20118933
PMCID:
PMC2835984
See all PubMed Citations (6)

Details of each submission

From Invitae, SCV001236133.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (6)

Description

This variant results in the deletion of part of exon 14 (c.1295_1298+6del) of the PNKP gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in PNKP are known to be pathogenic (PMID: 20118933, 25728773). This variant is present in population databases (rs587784366, gnomAD 0.03%). This variant has been observed in individual(s) with PNKP-related conditions (PMID: 31167812). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 159788). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. Experimental studies have shown that this variant affects PNKP function (PMID: 32504494). For these reasons, this variant has been classified as Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: May 1, 2024