Fetal anomalies
Gene: POLE

POLE (DNA polymerase epsilon, catalytic subunit)
EnsemblGeneIds (GRCh38): ENSG00000177084
EnsemblGeneIds (GRCh37): ENSG00000177084
OMIM: 174762, Gene2Phenotype
POLE is in 10 panels

3 reviews

Arina Puzriakova (Genomics England Curator)

The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Created: 3 Mar 2022, 11:19 a.m. | Last Modified: 3 Mar 2022, 11:19 a.m.

Panel Version: 1.836

Created: 3 Mar 2022, 11:19 a.m.
Last Modified: 3 Mar 2022, 11:19 a.m.
Panel version: 1.836

Catherine Snow (Genomics England)

Comment on list classification: Change from Green to Amber, as requested by NHSE for signed-off panel.
Created: 19 Aug 2020, 6:21 p.m. | Last Modified: 19 Aug 2020, 6:21 p.m.

Panel Version: 1.85

Created: 19 Aug 2020, 6:21 p.m.
Last Modified: 19 Aug 2020, 6:21 p.m.
Panel version: 1.85

Rebecca Foulger (Genomics England curator)

Comment on list classification: Originally added to panel as Amber based on PMID:30503519. Updated rating from Amber to Green with curation of additional paper PMID:25948378 who report a separate individual with IUGR. Phenotype relevant to panel, and sufficient evidence to support causation.
Created: 29 Apr 2020, 7:56 p.m. | Last Modified: 29 Apr 2020, 7:57 p.m.

Panel Version: 1.26

PMID:25948378 (Thiffault et al., 2015) report a girl homozygous for a splice variant in POLE1 (c.4444 + 3A > G). Fetal anomalies on the ultrasound included intrauterine growth restriction, short long bones, suspected skull abnormalities nad oligohydamnios.
Created: 29 Apr 2020, 7:53 p.m. | Last Modified: 29 Apr 2020, 7:53 p.m.

Panel Version: 1.22

Added to panel based on prenatal phenotype reported in PMID:30503519: (Logan et al., 2018) report biallelic variants in POLE in 15 indivs from 12 families (mix of countries). All subjects shared the same intronic variant (c.1686+32C>G) as part of a common haplotype, in combination with different loss-of-function variants in trans. Phenotypically, affected individuals all had IUGR and severe growth failure of prenatal onset.
Sources: Literature
Created: 29 Apr 2020, 4:36 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
IUGR; severe growth failure of prenatal onset

Publications

23230001

Created: 29 Apr 2020, 4:36 p.m.
Last Modified: 29 Apr 2020, 7:57 p.m.
Panel version: 1.22

Details

Mode of Inheritance

BIALLELIC, autosomal or pseudoautosomal

Sources

Expert Review Green
Literature

Phenotypes

IUGR
severe growth failure of prenatal onset
FILS syndrome, 615139
facial dysmorphism, immunodeficiency, livedo, and short stature (FILS)

OMIM

174762

Clinvar variants

Variants in POLE

Penetrance

None

Publications

Panels with this gene

History Filter Activity

3 Mar 2022, Gel status: 3

Removed Tag

Arina Puzriakova (Genomics England Curator)

Tag for-review was removed from gene: POLE.

3 Mar 2022, Gel status: 3

Added New Source, Status Update

Arina Puzriakova (Genomics England Curator)

Source Expert Review Green was added to POLE. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)

20 Aug 2020, Gel status: 2

Added Tag

Sarah Leigh (Genomics England Curator)

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

19 Aug 2020, Gel status: 2

Entity classified by Genomics England curator

Catherine Snow (Genomics England)

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

29 Apr 2020, Gel status: 3