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Xp21.2 region (includes NR0B1) Gain
ISCA-46302-Gain 2

Fetal anomalies
Gene: LMNB2

LMNB2 (lamin B2)
EnsemblGeneIds (GRCh38): ENSG00000176619
EnsemblGeneIds (GRCh37): ENSG00000176619
OMIM: 150341, Gene2Phenotype
LMNB2 is in 5 panels

5 reviews

Achchuthan Shanmugasundram (Genomics England Curator)

After NHS Genomic Medicine Service consideration, the mode of inheritance of this gene has not been changed and remains MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted.

The GMS reviewers noted as follows:
Pathogenic monoallelic missense variants are causative of primary microcephaly. Homozygous loss-of-function variant reported in two related newborns with severe brain development abnormalities and perinatal death, phenotype consistent with Lmnb2-deficient mouse models (PMID:40011009). At least one further unrelated case is required to confirm an additional biallelic loss-of-function mechanism for LMNB2-related disease (mechanism of pathogenicity for monoallelic variants is uncertain).
Created: 11 Mar 2026, 7:08 p.m. | Last Modified: 11 Mar 2026, 7:29 p.m.

Panel Version: 6.157

Created: 11 Mar 2026, 7:08 p.m.
Last Modified: 11 Mar 2026, 7:29 p.m.
Panel version: 6.157

Sarah Leigh (Genomics England Curator)

Green List (high evidence)

PMID: 40011009 reports two related babies who were homozygous for a loss-of-function LMNB2 variant. Both babies shared a similar phenotype of severe brain development abnormalities and died during the perinatal period. This shared phenotype was reflected in several Lmnb2-deficient mouse models.
Material from the patient’s fibroblasts (obtained at birth) were used in Western blot and immunofluorescence cell labelling, and confirmed the complete absence of lamin B2 and revealed an increase in lamin B1, together with alterations in alpha-tubulin and vimentin organisation. (PMID: 40011009).
Created: 9 Apr 2025, 10:27 a.m. | Last Modified: 9 Apr 2025, 10:28 a.m.

Panel Version: 5.90

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Created: 9 Apr 2025, 10:27 a.m.
Last Modified: 9 Apr 2025, 10:28 a.m.
Panel version: 5.90

Sarah Graham (West Midlands Regional Genetics Laboratory, Birmingham Women's and Children’s NHS Foundation Trust)

Green List (high evidence)

Amend MOI to both monoallelic and biallelic. Homozygous loss-of-function variant in the LMNB2 gene reported in two related newborns severe brain development abnormalities and perinatal death, phenotype consistent with Lmnb2-deficient mouse models (PMID: 40011009).
Created: 2 Apr 2025, 10:35 a.m. | Last Modified: 2 Apr 2025, 10:35 a.m.

Panel Version: 5.87

Mode of inheritance
BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal

Publications

PMID: 40011009

Created: 2 Apr 2025, 10:35 a.m.
Last Modified: 2 Apr 2025, 10:35 a.m.
Panel version: 5.87

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

Comment on list classification: Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'Q4_21_rating' tag)
Created: 3 Nov 2021, 2:04 p.m. | Last Modified: 3 Nov 2021, 2:04 p.m.

Panel Version: 1.775

Created: 3 Nov 2021, 2:04 p.m.
Last Modified: 3 Nov 2021, 2:04 p.m.
Panel version: 1.836

Rhiannon Mellis (Great Ormond Street Hospital)

This gene and phenotype were reviewed during a meeting on 21st October 2021 between representatives of the North Thames and Central & South R21 testing GLHs.

Clinical review and curation was performed by Lyn Chitty, Alison Male, Rowenna Roberts, Rhiannon Mellis (North Thames GLH) and Stephanie Allen, Denise Williams and Esther Kinning (Central & South GLH).

Outcome of review: Confirmed that the phenotype is fetally relevant, support adding to the Fetal anomalies panel as a Green gene.

Already rated Green on the following other PanelApp panel(s): Severe microcephaly (pending)

Details of review:
Parry et al 2020 (PMID: 33033404) report on a cohort from DDD and 100k genomes studies: 13 individuals with heterozygous variant in LMNB1 (N=7) and LMNB2 (N=6) - phenotype of severe congenital microcephaly and ID (otherwise non-syndromic).
Sources: Expert Review, Literature
Created: 29 Oct 2021, 3:46 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Microcephaly 27, primary, autosomal dominant

Publications

PMID: 33033404

Created: 29 Oct 2021, 3:46 p.m.

Panel version: 1.749

Details

Mode of Inheritance

MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Sources

Expert Review Green

Phenotypes

Microcephaly 27, primary, autosomal dominant, OMIM:619180
microcephaly 27, primary, autosomal dominant, MONDO:0030929

OMIM

150341

Clinvar variants

Variants in LMNB2

Penetrance

None

Publications

Panels with this gene

History Filter Activity

11 Mar 2026, Gel status: 3

Removed Tag, Removed Tag

Achchuthan Shanmugasundram (Genomics England Curator)

Tag Q2_25_ MOI was removed from gene: LMNB2. Tag Q2_25_ NHS_review was removed from gene: LMNB2.

9 Apr 2025, Gel status: 3

Added Tag, Added Tag

Sarah Leigh (Genomics England Curator)

Tag Q2_25_ MOI tag was added to gene: LMNB2. Tag Q2_25_ NHS_review tag was added to gene: LMNB2.

9 Apr 2025, Gel status: 3

Set Phenotypes

Sarah Leigh (Genomics England Curator)

Phenotypes for gene: LMNB2 were changed from Microcephaly 27, primary, autosomal dominant, OMIM:619180 to Microcephaly 27, primary, autosomal dominant, OMIM:619180; microcephaly 27, primary, autosomal dominant, MONDO:0030929

9 Apr 2025, Gel status: 3

Set publications

Sarah Leigh (Genomics England Curator)

Publications for gene: LMNB2 were set to 33033404

3 Mar 2022, Gel status: 3