Severe microcephaly
Gene: ANKLE2The rating of this gene has been updated following NHS Genomic Medicine Service approval.Created: 10 Mar 2022, 10:52 a.m. | Last Modified: 10 Mar 2022, 10:52 a.m.
Panel Version: 2.282
Comment on list classification: Upgraded from Red to Amber, but there is enough evidence to rate Green at the next GMS panel update (added 'for-review' tag).
At least 5 individuals from 4 unrelated families with primary microcephaly (HC -4.33 to -16.30 SD) and biallelic variants in ANKLE2 (PMIDs: 25259927 and 30214071). Several lines of supporting evidence using Drosophila Ankle2 mutants, including reduced brain size which could be rescued by expression of wildtype human ANKLE2.
This gene-disease association is also listed in OMIM (MIM# 616681).Created: 27 Jan 2021, 11:44 a.m. | Last Modified: 27 Jan 2021, 11:44 a.m.
Panel Version: 2.83
Four families reported, two share the same homozygous variant. Functional data.Created: 30 Aug 2020, 5:37 a.m. | Last Modified: 30 Aug 2020, 5:37 a.m.
Panel Version: 2.19
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Microcephaly 16, primary, autosomal recessive, MIM# 616681
Publications
Variants in this GENE are reported as part of current diagnostic practice
As discussed with the GMS Neurology Specialist Test Group webex call 11thJuly 2019: The Specialist Test Group all agreed that there is only enough evidence to rate this gene RedCreated: 29 Jul 2019, 4:18 p.m. | Last Modified: 29 Jul 2019, 4:18 p.m.
Panel Version: 1.62
Only reported in one familyCreated: 12 Jan 2017, 11:31 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
?Microcephaly 16, primary, autosomal recessive 616681
Publications
Tag for-review was removed from gene: ANKLE2.
Source Expert Review Green was added to ANKLE2. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Tag for-review tag was added to gene: ANKLE2.
Phenotypes for gene: ANKLE2 were changed from ?Microcephaly 16, primary, autosomal recessive, 616681 to Microcephaly 16, primary, autosomal recessive, OMIM:616681; Microcephaly 16, primary, autosomal recessive, MONDO:0014730
Publications for gene: ANKLE2 were set to 25259927
Gene: ankle2 has been classified as Amber List (Moderate Evidence).
Source NHS GMS was added to ANKLE2.
2nd March 2017: Panel review was assessed and panel was revised according to expert review and additional curation. This panel began with an expert gene list from Professor Andrew Jackson (University of Edinburgh) for primary microcephaly (MCPH) and microcephalic primordial dwarfism (MPD). Other disorders are included where microcephaly is a primary feature. Disorders where microcephaly is not the primary presenting feature are not included (e.g. congenital disorders of glycosylation, Proud syndrome, Norrie disease). The panel does not include disorders with a cortical malformation (e.g. lissencephaly) since the Malformations of cortical development' panel would be applied to these patients.
This gene has been classified as Red List (Low Evidence).
Publications for ANKLE2 were set to 25259927
ANKLE2 was added to Primary Microcephaly - Microcephalic Dwarfism Spectrumpanel. Sources: Other
ANKLE2 was created by rfoulger