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Hereditary neuropathy NOT PMP22 copy number

Gene: PNKP

Amber List (moderate 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)

Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Created: 25 Jan 2021, 2:49 p.m. | Last Modified: 25 Jan 2021, 2:49 p.m.
Panel Version: 1.21
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, 2:48 p.m. | Last Modified: 25 Jan 2021, 2:48 p.m.
Panel Version: 1.19

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, 6:41 a.m. | Last Modified: 13 Jan 2021, 6:41 a.m.
Panel Version: 1.19

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

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

Gene rated Amber : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart): Extension of panel scope but limited evidence / Broader phenotype: good evidence for ataxia/oculomotor apraxia, less for more severe phenotype
Created: 7 Dec 2019, 12:03 a.m. | Last Modified: 7 Dec 2019, 12:03 a.m.
Panel Version: 0.86
This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) 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, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.
Created: 6 Dec 2019, 10:25 p.m. | Last Modified: 6 Dec 2019, 10:25 p.m.
Panel Version: 0.84
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 Amber
  • London North GLH
  • NHS GMS
  • NHS GMS
  • London North GLH
Phenotypes
  • Microcephaly, global developmental delay, progressive cerebellar ataxia and atrophy, sensory-motor axonal neuropathy
  • Microcephaly, seizures, and developmental delay, 613402
  • Ataxia-oculomotor apraxia 4, 616267
Tags
for-review
OMIM
605610
Clinvar variants
Variants in PNKP
Penetrance
None
Publications
Panels with this gene

History Filter Activity

25 Jan 2021, Gel status: 2

Added Tag

Sarah Leigh (Genomics England Curator)

Tag for-review tag was added to gene: PNKP.

25 Jan 2021, Gel status: 2

Entity classified by Genomics England curator

Sarah Leigh (Genomics England Curator)

Gene: pnkp has been classified as Amber List (Moderate Evidence).

25 Jan 2021, Gel status: 2

Set publications

Sarah Leigh (Genomics England Curator)

Publications for gene: PNKP were set to 30039206

6 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)

5 Dec 2019, Gel status: 1

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes

Ellen McDonagh (Genomics England Curator)

gene: PNKP was added gene: PNKP was added to Hereditary neuropathy NOT PMP22 copy number. Sources: NHS GMS,London North GLH Mode of inheritance for gene: PNKP was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PNKP were set to 30039206 Phenotypes for gene: PNKP were set to Microcephaly, global developmental delay, progressive cerebellar ataxia and atrophy, sensory-motor axonal neuropathy; Microcephaly, seizures, and developmental delay, 613402; Ataxia-oculomotor apraxia 4, 616267