Intellectual disability
Gene: NHLRC2

NHLRC2 (NHL repeat containing 2)
EnsemblGeneIds (GRCh38): ENSG00000196865
EnsemblGeneIds (GRCh37): ENSG00000196865
NHLRC2 is in 5 panels

1 review

Achchuthan Shanmugasundram (Genomics England Curator)

Green List (high evidence)

Comment on list classification: There is sufficient evidence available (>15 unrelated cases with moderate/ severe GDD/ ID) for the promotion of this gene to green rating in the next GMS update.
Created: 22 Mar 2025, 2:08 p.m. | Last Modified: 22 Mar 2025, 2:08 p.m.

Panel Version: 8.166

Comment on publications: PMID:39328589 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.
Created: 22 Mar 2025, 2:06 p.m. | Last Modified: 22 Mar 2025, 2:06 p.m.

Panel Version: 8.165

PMID:37188825 reported 15 patients ranging in age from 22 months to 19 years, from 12 unrelated families with an overlapping phenotype with FINCA syndrome (MIM #618278). They were identified with nine novel NHLRC2 variants via exome sequencing. All these patients presented with moderate to severe global developmental delay and variable disease progression. Seizures, truncal hypotonia and movement disorders were also frequently observed.

PMID:39328589 reported two siblings of Chinese decent with FINCA syndrome and they were identified with the same compound heterozygous variants in NHLRC2 gene. Both of them presented with developmental delay, of which the younger brother was evaluated with a development quotient (DQ) of 39 at four months of age (normal range >85), indicating moderate intellectual disability.

This gene has also been associated with relevant phenotype on the DD panel of Gene2Phenotype, with a definitive rating.
Sources: Literature
Created: 22 Mar 2025, 2:01 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
FINCA syndrome, OMIM:618278

Publications

Created: 22 Mar 2025, 2:01 p.m.

Panel version: 8.164

Details

Mode of Inheritance

BIALLELIC, autosomal or pseudoautosomal

Sources

Expert Review Amber
Literature

Phenotypes

FINCA syndrome, OMIM:618278

Tags

gene-checked Q1_25_ promote_green

Clinvar variants

Variants in NHLRC2

Penetrance

None

Publications

Panels with this gene