Genes in panel

Hereditary neuropathy

Gene: PNKP

Green List (high evidence)

PNKP (polynucleotide kinase 3'-phosphatase)
EnsemblGeneIds (GRCh38): ENSG00000039650
EnsemblGeneIds (GRCh37): ENSG00000039650
OMIM: 605610, Gene2Phenotype
PNKP is in 13 panels

4 reviews

Sarah Leigh (Genomics England Curator)

Green List (high evidence)

Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen, although variants PNKP have been given a confirmed classification in Gen2Phen for Ataxia-oculomotor apraxia 4 (OMIM:616267). At least 2 variants were reported: rs774995635, was homozygous in 5 affected members of a large Costa Rican family (18 affected members, but only 5 were sequenced) and heterozygous in the mother of one of the affected subjects who was sequenced (PMID 30039206). Compound heterozygous rs774995635 and rs770849181 were reported in five unrelated Costa Rican cases, although it was reported that there appeared to be a ancestral founder haplotype for the rs770849181 (PMID 30039206). A further case was reported where a 17year old with axonal Charcot-Marie-Tooth disease was homozygous and his parents were heterozygous for rs770849181 (PMID 27066567).
Created: 25 Jan 2021, 2:47 p.m. | Last Modified: 25 Jan 2021, 2:47 p.m.
Panel Version: 1.381

Publications

Dmitrijs Rots (RadboudUMC)

Green List (high evidence)

In PMID: 30039206 reported a homozygous nonsense variant in a large Costa Rican family segregating with CMT2 phenotype. Additional 5 cases with compound heterozygous nonsense variants and CMT2 phenotype also reported. Some patients have Ataxia, but not oculomotor apraxia or Microcephaly, seizures, and developmental delay.
Created: 13 Jan 2021, 6:38 a.m. | Last Modified: 13 Jan 2021, 6:41 a.m.
Panel Version: 1.381

Phenotypes
Polyneuropathy; ataxia

Publications

Variants in this GENE are reported as part of current diagnostic practice

Louise Daugherty (Genomics England Curator)

I don't know

The Neurology Specialist Test Group agreed that this gene was recommended for the WGS panel based on a broader phenotype view to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP. This panel includes conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation. This panel as going to be used for R78, but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy and as a result a new panel was created https://panelapp.genomicsengland.co.uk/panels/846/ for this purpose.
Created: 7 Dec 2019, 6:08 p.m. | Last Modified: 7 Dec 2019, 6:08 p.m.
Panel Version: 1.352
Review and rating uploaded from file (Curation_Template_GMS_Neuro_AR_20190521.xlsx) submitted by Alex Rossor (UCL Institute of Neurology) on behalf of London North GLH for GMS Neurology specialist test group.
Created: 11 Jun 2019, 1:40 p.m.

Alexander Rossor (UCL Institute of Neurology)

Green List (high evidence)

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Microcephaly, global developmental delay, progressive cerebellar ataxia and atrophy, sensory-motor axonal neuropathy

Publications

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • NHS GMS
  • London North GLH
Phenotypes
  • ?Charcot-Marie-Tooth disease, type 2B2 605589
  • Ataxia-oculomotor apraxia 4 OMIM:616267
  • Microcephaly, seizures, and developmental delay OMIM:613402
OMIM
605610
Clinvar variants
Variants in PNKP
Penetrance
None
Publications
Panels with this gene

History Filter Activity

25 Jan 2021, Gel status: 3

Set Phenotypes

Sarah Leigh (Genomics England Curator)

Phenotypes for gene: PNKP were changed from Ataxia-oculomotor apraxia 4, 616267; Microcephaly, seizures, and developmental delay, 613402; Microcephaly, global developmental delay, progressive cerebellar ataxia and atrophy, sensory-motor axonal neuropathy to ?Charcot-Marie-Tooth disease, type 2B2 605589; Ataxia-oculomotor apraxia 4 OMIM:616267; Microcephaly, seizures, and developmental delay OMIM:613402

25 Jan 2021, Gel status: 3

Entity classified by Genomics England curator

Sarah Leigh (Genomics England Curator)

Gene: pnkp has been classified as Green List (High Evidence).

7 Dec 2019, Gel status: 2

Added New Source, Status Update

Louise Daugherty (Genomics England Curator)

Source Expert Review Amber was added to PNKP. Rating Changed from Red List (low evidence) to Amber List (moderate evidence)

6 Jun 2019, Gel status: 1

Set Phenotypes

Louise Daugherty (Genomics England Curator)

Phenotypes for gene: PNKP were changed from to Ataxia-oculomotor apraxia 4, 616267; Microcephaly, seizures, and developmental delay, 613402; Microcephaly, global developmental delay, progressive cerebellar ataxia and atrophy, sensory-motor axonal neuropathy

6 Jun 2019, Gel status: 1

Set publications

Louise Daugherty (Genomics England Curator)

Publications for gene: PNKP were set to

6 Jun 2019, Gel status: 1

Set mode of inheritance

Louise Daugherty (Genomics England Curator)

Mode of inheritance for gene: PNKP was changed from to BIALLELIC, autosomal or pseudoautosomal

6 Jun 2019, Gel status: 1

Added New Source

Louise Daugherty (Genomics England Curator)

Source NHS GMS was added to PNKP.

6 Jun 2019, Gel status: 1

Created, Added New Source, Set mode of inheritance

Louise Daugherty (Genomics England Curator)

gene: PNKP was added gene: PNKP was added to Hereditary neuropathy. Sources: London North GLH Mode of inheritance for gene: PNKP was set to