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Intellectual disability

Gene: BCORL1

Amber List (moderate evidence)

BCORL1 (BCL6 corepressor like 1)
EnsemblGeneIds (GRCh38): ENSG00000085185
EnsemblGeneIds (GRCh37): ENSG00000085185
OMIM: 300688, Gene2Phenotype
BCORL1 is in 3 panels

6 reviews

Zornitza Stark (Australian Genomics)

Green List (high evidence)

Four unrelated families reported with variable ID, now has OMIM#, and original variant no longer listed as VOUS.
Created: 29 Jan 2020, 10:25 a.m. | Last Modified: 29 Jan 2020, 10:25 a.m.
Panel Version: 3.0

Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females

Phenotypes
Shukla-Vernon syndrome, MIM# 301029

Publications

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

Rebecca Foulger (Genomics England curator)

Comment on list classification: Updated rating from Red to Amber based on external review by Konstantinos Varvagiannis and the new paper Shukla et al., 2019 (PMID:30941876). The original Asn820Ser variant from Schuurs-Hoeijmakers et al., 2013 (PMID:24123876) is still listed as a VUS in OMIM due to a lack of evidence for association with the ID phenotype. Although Shukla et al report 3 cases with 3 new BCORL1 variants (two unrelated males and a further three brothers), patient 2 does not have ID, but instead has typical early motor milestones, and speech delay. ID is also mild in Patient 1. Based on 2 clear cases plus 1 potential case from Shukla et al,. I have rated Amber and added a 'watchlist' tag awaiting further reports.
Created: 6 Jun 2019, 10:27 a.m.

Konstantinos Varvagiannis (Other)

I don't know

This gene may be considered for upgrade probably to amber (or green).

Schuurs-Hoeijmakers et al. (2013 - PMID: 24123876) reported briefly on 2 males with hypotonia, severe ID and similar facial features. Both harbored a BCORL1 missense variant (NM_021946.4:c.2459A>G or p.Asn820Ser) inherited from their (probably) unaffected mother (X-linked gene). The authors comment that BCORL1 encodes a transcriptional corepressor interacting with class II histone acetyltransferases and deacetylases and appears to be expressed in brain/neuronal tissue.

Shukla et al. (2019 - PMID: 30941876) report on 5 males from 3 families with DD, ID (4/5 - in 1 individual mild, in 3 further sibs severe), ASD (5/5) or additional behavioral abnormalities and/or some other possibly overlapping features. All individuals were found to be hemizygous for BCORL1 missense variants (in all cases inherited). The following variants were reported : c.2345T>A or p.Val782Glu, c.1487C>T or p.Ser496Phe and c.95C>T or p.Pro32Leu (NM_021946.4). The mother of one subject (with mild ID) had some degree of learning disabilities, anxiety and ADHD. One individual without apparent ID had inherited the variant from his mother who had normal educational attainment.

There are no functional studies (or X-inactivation studies in females) performed in any of these articles.

BCORL1 is not associated with any phenotype in OMIM/G2P. The gene is included in gene panels for intellectual disability offered by several diagnostic laboratories (incl. Radboud UMC).
Created: 14 Apr 2019, 6:07 p.m.

Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)

Phenotypes
Global developmental delay; Intellectual disability; Autism; Behavioral abnormality

Publications

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

Sarah Leigh (Genomics England Curator)

Red List (low evidence)

Not associated with phenotype in OMIM or G2P. One variant reported as a heterozygote in two brothers with severe intellectual disability, however also present in unaffected mother, therefore classes as a VUS
Created: 15 Dec 2017, 9:38 a.m.

Mode of inheritance
Unknown

Publications

Caroline Wright (Sanger)

Red List (low evidence)

Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)

Lu Raymond (university of cambridge )

Red List (low evidence)

Details

Mode of Inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Sources
Phenotypes
  • Intellectual disability, developmental delay and dysmorphism
  • Behavioral abnormality
Tags
watchlist
OMIM
300688
Clinvar variants
Variants in BCORL1
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

6 Jun 2019, Gel status: 2

Added Tag

Rebecca Foulger (Genomics England curator)

Tag watchlist tag was added to gene: BCORL1.

6 Jun 2019, Gel status: 2

Entity classified by Genomics England curator

Rebecca Foulger (Genomics England curator)

Gene: bcorl1 has been classified as Amber List (Moderate Evidence).

6 Jun 2019, Gel status: 1

Set publications

Rebecca Foulger (Genomics England curator)

Publications for gene: BCORL1 were set to 24123876; 24896178; 26350204

6 Jun 2019, Gel status: 1

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for gene: BCORL1 were changed from to Intellectual disability, developmental delay and dysmorphism; Behavioral abnormality

6 Jun 2019, Gel status: 1

Set mode of inheritance

Rebecca Foulger (Genomics England curator)

Mode of inheritance for gene: BCORL1 was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)

12 Mar 2018, Gel status: 1

Panel promoted to version 2.0

Ellen McDonagh (Genomics England Curator)

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.

5 Jan 2018, Gel status: 1

Set mode of inheritance, Set publications

Ellen McDonagh (Genomics England Curator)

Model of inheritance for gene BCORL1 was set to Unknown Publications for gene BCORL1 was set to ['24123876', ' 24896178', ' 26350204']

13 Nov 2015, Gel status: 1

gel status update

GEL ()

The Gel status was updated for this whole panel

13 Nov 2015, Gel status: 2

gel status update

GEL ()

The Gel status was updated for this whole panel

13 Nov 2015, Gel status: 0

Added New Source

Ellen McDonagh (Genomics England Curator)

BCORL1 was added to Intellectual disabilitypanel. Sources: Expert Review Red

13 Nov 2015, Gel status: 0

Created

Ellen McDonagh (Genomics England Curator)

BCORL1 was created by ellenmcdonagh