Intellectual disability - microarray and sequencing
Gene: NR2F2
Comment on list classification: There is sufficient evidence for this gene to be promoted to green rating in the next GMS review.Created: 13 Sep 2023, 12:48 p.m. | Last Modified: 13 Sep 2023, 12:48 p.m.
Panel Version: 5.277
This gene is an established gene for congenital heart defects (MIM #615779) and disorder of sexual differentiation (MIM #618901). This gene has been associated with these two phenotypes in both OMIM and Gene2Phenotype. Some patients with CHD (MIM #615779) are reported with developmental delays in the OMIM record.
PMID:29663647 - An 11-month old boy was reported with global developmental delay, dysmorphic features, coarctation of the aorta, and ventricular septal defect and was identified with pathogenic NR2F2 variant.
PMID:37500725 - 16 previously unreported unrelated individuals (and a mildly affected mosaic mother of one of them) with rare heterozygous variants (majority are de novo variants) were reviewed in this publication and they had variable clinical presentations including intrauterine growth restriction (IUGR), CHD, CDH, genital anomalies, DSD, developmental delays, hypotonia, feeding difficulties, failure to thrive, congenital and acquired microcephaly, dysmorphic facial features, renal failure, hearing loss, strabismus, asplenia, and vascular malformations. All 14 for whom data is available had motor delays and 13 had speech delay. One of them had global developmental delay, one had mild intellectual disability and four had learning disabilities.Created: 13 Sep 2023, 12:37 p.m. | Last Modified: 13 Sep 2023, 12:46 p.m.
Panel Version: 5.276
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications
Recent publication Eur J Hum Genet
. 2023 Jul 27. doi: 10.1038/s41431-023-01434-5. Online ahead of print.
Heterozygous rare variants in NR2F2 cause a recognizable multiple congenital anomaly syndrome with developmental delaysCreated: 5 Sep 2023, 2:53 p.m. | Last Modified: 5 Sep 2023, 2:53 p.m.
Panel Version: 5.271
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
intrauterine growth restriction (IUGR); CHD; CDH; genital anomalies; DSD; developmental delays; hypotonia; feeding difficulties; failure to thrive; congenital and acquired microcephaly; dysmorphic facial features; renal failure; hearing loss; strabismus; asplenia; vascular malformations
Publications
Following discussion with the clinical team, this gene has been demoted from Amber to Red, in accordance with the external review by Zornitza StarkCreated: 17 Aug 2020, 10:09 a.m. | Last Modified: 17 Aug 2020, 10:09 a.m.
Panel Version: 3.253
ID is not part of the phenotype.Created: 6 Mar 2020, 3:51 a.m. | Last Modified: 6 Mar 2020, 3:51 a.m.
Panel Version: 3.3
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Congenital heart defects, multiple types, 4, MIM# 615779
This is a pertinent gene from the NIHR BioResource - Rare Diseases Study (NIHRBR-RD) BRIDGE Study : SPEED (Specialist Pathology: Evaluating Exomes in Diagnostics) which covers epilepsies, movement and microcephaly disorders, this gene is on the SPEED_NEURO_20170705 gene list. Evidences used for SPEED NEURO gene list: in_ddg2p_20141118_conf;in_ddg2p_20141118_conf;in_ddg2p_201507;in_ddg2p_201507_conf;in_ddg2p_2_4_2017;in_ddg2p_2_4_2017_conf . Main mutation mechanism : Loss of functionCreated: 27 Jul 2017, 7:51 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications
Comment on list classification: This gene is from an expert list and needs further assessment by the Genomics England curation team to access inclusion and pertinence to this panel.Created: 28 Jul 2017, 3:02 p.m.
Tag Q3_23_promote_green tag was added to gene: NR2F2. Tag Q3_23_NHS_review tag was added to gene: NR2F2.
Gene: nr2f2 has been classified as Amber List (Moderate Evidence).
Gene: nr2f2 has been classified as Amber List (Moderate Evidence).
Publications for gene: NR2F2 were set to 29663647; 37500725
Publications for gene: NR2F2 were set to 29663647; 37500725
Publications for gene: NR2F2 were set to
Mode of inheritance for gene: NR2F2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mode of inheritance for gene: NR2F2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mode of inheritance for gene: NR2F2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mode of inheritance for gene: NR2F2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Source Expert Review Red was added to NR2F2. Rating Changed from Amber List (moderate evidence) to Red List (low evidence)
12.03.2018: Due to major updates completed (Phase 1, 2 and 3), this panel was promoted to Version 2 in order to reflect the major updates since November 2017 which have resulted in reviews for 836 genes added by Genomics England Curators and the Clinical Team, 130 new Green genes added to the interpretation pipeline (from 751 to 881 Green genes), and the gene total has increased from 1879 to 1927.
This gene has been classified as Amber List (Moderate Evidence).
NR2F2 was added to Intellectual disabilitypanel. Sources: BRIDGE study SPEED NEURO Tier1 Gene
NR2F2 was created by BRIDGE