By harmonizing functional data for 9,424 BRCA1 and BRCA2 missense variants and applying ClinGen guidelines, Lyra, Jr. et al. establish an integrated framework whose pathogenicity assignments track wit...

Eleven individuals homozygous for C-terminally truncating BRIP1 variants do not exhibit symptoms of Fanconi anemia. Droste et al. characterize the cellular phenotype, demonstrating that a functional N...

Meyer-Schuman et al. interrogate MECP2 cis-regulatory elements (CREs) using a high-throughput reporter assay. This work identifies transcription factor binding sites that regulate MECP2 expression and...

Meyer-Schuman et al. interrogate MECP2 cis-regulatory elements (CREs) using a high-throughput reporter assay. This work identifies transcription factor binding sites that regulate MECP2 expression and...

Hypomorphic variants in IDUA are associated with attenuated mucopolysaccharidosis type 1, including apparent non-syndromic retinitis pigmentosa. Functional experiments are used to characterize the imp...

Polygenic risk and family history each independently predict coronary heart disease. In two diverse US cohorts, Naderian et al. show that adding both to the pooled cohort equations improves risk…

Heterozygous carriers of autosomal recessive disease variants are often considered clinically unaffected, yet population biobanks can reveal measurable carrier phenotypes. MMACHC (MIM: 609831) encodes...

ALLSPICE tests whether rare variants within gene-burden associations have proportional effects across phenotypes. Applied to cross-phenotype burden associations, it identified ALB missense variants wi...

Macintosh et al. describe a rapid and scalable pipeline integrating clinical diagnostics, generation of stem cells and neurons, and in vitro screening of genetic therapies for neurodevelopmental disor...

AI-MARRVEL helped identify rare BRSK1 variants linked to a neurodevelopmental disorder, with fruit fly studies revealing their effects on neurons.

Researchers at Baylor College of Medicine, the Duncan Neurological Research Institute (Duncan NRI) at Texas Children’s Hospital, the Texome Project and...

BRSK1 is required for neural development, but its role in human disease is poorly understood. We report 10 individuals with seven BRSK1 variants who exhibit neurodevelopmental delay, sometimes accompa...

CanVar-UK is a data sharing and variant interpretation platform for cancer susceptibility genes (CSGs) housing in silico, functional, case/control frequency, and multifactorial data for over 1.1 milli...

Clinical genetic data are increasingly central to diagnosis and treatment, yet Canadian laboratories lack practical guidance for sharing them responsibly. This CCMG position statement translates ethic...

Li et al. identify robust cis-by-trans epistatic interactions in the human plasma proteome. They uncover an ABO-centered epistatic regulatory network where blood type modifies cis-genetic effects on p...

Researchers at Baylor College of Medicine and Texas Children Hospital’s Duncan Neurological Research Institute (Duncan NRI) have identified a rare genetic...

Mok et al. identify a recurrent de novo missense variant, c.1126G>A (p.Glu376Lys), in BMPR2 in individuals presenting with neurodevelopmental symptoms. Using Drosophila functional assays, they show th...

This perspective summarizes early experiences from genomic newborn screening studies, totaling over 10,800 infants from the US, Belgium, and Australia. While these provide data on technical feasibilit...

Age-related hearing loss can arise through different biological mechanisms. By integrating human genome-wide association data with single-cell gene expression profiles, we show that genes associated w...

Researchers discovered how a common lupus risk variant may boost antiviral defenses while increasing autoimmunity risk.

Virolainen et al. combine human genetics, functional genomics, and mouse models to show that a common lupus-risk IRF7 haplotype enhances IRF7 nuclear localization, DNA binding, and type I interferon production. The haplotype improves antiviral defense but increases autoreactivity, revealing an evolutionary trade-off between host protection and autoimmunity.

CanVar-UK is a data sharing and variant interpretation platform for cancer susceptibility genes (CSGs) housing in silico, functional, case/control frequency, and multifactorial data for over 1.1 milli...

At 9q34.13, melanoma and nevus risk-associated variants regulate RAPGEF1 and UCK1 expression in melanocytes. Functional studies showed that RAPGEF1 promotes melanocyte growth and RAS activation and is...

Genes associated with rare neurodevelopmental disorders are still being identified. The authors identify ZNF536 as a developmental disease-associated gene, describing a cohort of affected individuals ...

Complex traits differ widely in how many genetic variants shape them. Fuhrer et al. show that this is mirrored in where heritability sits in the genome, shifting from exons toward distal intergenic re...

A JAX-led study of more than 5,000 people is challenging long-held assumptions about cerebral palsy genetics.