Siddharth Banka

Guidance for clinical variant classification in genes for spliceosomal small nuclear RNAs

The paper provides guidance for classifying variants in snRNA genes and introduces RNUdb, a tool to support variant annotation and classification.

De novo EHMT2 variants cause an autosomal dominant EHMT2-related Kleefstra syndrome via loss of G9a methyltransferase activity.

The paper identifies de novo EHMT2 variants causing an autosomal dominant Kleefstra syndrome by impairing G9a methyltransferase activity, mimicking EHMT1 haploinsufficiency.

Systematic analysis of homozygous autosomal copy number losses in exomes improves diagnostic yield and uncovers ultra-rare recessive disorders

The paper systematically analyzes homozygous autosomal copy number losses in exomes to improve diagnostic yield and identify ultra-rare recessive disorders.

Biallelic variants in RNU2-2 cause a remarkably frequent developmental epileptic encephalopathy

The paper identifies biallelic variants in RNU2-2 as a frequent cause of a severe developmental epileptic encephalopathy, distinct from a dominant disorder, and links them to reduced U2-2 abundance.

Genetic modifiers and ascertainment drive variable expressivity of complex disorders

The paper examines how modifier variants affect clinical outcomes in individuals with primary disease variants, showing context-dependent phenotypic associations and synergistic interactions.

Epigenome and transcriptome changes in KMT2D-related Kabuki syndrome Type 1 iPSCs, neuronal progenitors and cortical neurons

This study examines epigenome and transcriptome changes in KS1 iPSCs and neuronal differentiation stages, identifying altered H3K4 methylation and gene expression patterns.

Biallelic variants in the non-coding RNA gene RNU4-2 cause a recessive neurodevelopmental syndrome with distinct white matter changes

The paper identifies biallelic variants in RNU4-2 causing a recessive neurodevelopmental syndrome with distinct white matter changes, expanding the known genotypic and phenotypic spectrum of RNU4-2-related disorders.

Utility of genome sequencing and group-enrichment to support splice variant interpretation in Marfan syndrome

The paper identifies non-canonical FBN1 splice variants in undiagnosed Marfan syndrome families using genome sequencing and RNA testing, finding 20 candidate variants with significant enrichment in FTAAD cases.

Multiple and novel molecular mechanisms in TUBA1A-related tubulinopathy: insights from deep clinical and neuroradiological phenotyping.

The paper identifies novel TUBA1A variants and shows reduced penetrance of malformations of cortical development in tubulinopathies.

Loss of DOT1L disrupts neuronal transcription, behavior, and leads to a neurodevelopmental disorder

This study shows that partial loss of DOT1L causes transcriptional, morphological, and behavioral defects in neurons across multiple models.

Comprehensive reanalysis for CNVs in exome sequencing data from unsolved rare disease cases results in new diagnoses

The paper reanalyzes exome sequencing data from rare disease cases to identify previously undetected copy number variants, resulting in diagnoses for 51 families and partial explanations for 34 individuals.

Regional nonsense constraint offers clinical and biological insights into rare genetic disorders

The paper identifies regional nonsense constraint in the human genome using sequencing data, showing enriched de novo variants in constrained regions linked to rare diseases.

Analysis of R-loop forming regions identifies RNU2-2P and RNU5B-1 as neurodevelopmental disorder genes

The paper identifies RNU2-2P and RNU5B-1 as neurodevelopmental disorder genes by analyzing R-loop forming regions in rare disease cohorts.

Genetic Risk of Axonal Neuropathy Following Infection

The paper identifies biallelic RCC1 variants causing an acute axonal neuropathy triggered by infection, with mechanistic overlap with ALS and GBS.

Genomic and biological panoramas of non-muscle actinopathies

The paper analyzes clinical and mechanistic data from individuals with ACTB/ACTG1 variants to identify distinct disease phenotypes and molecular mechanisms of non-muscle actinopathies.

Biallelic variants in DAP3 result in reduced assembly of the mitoribosomal small subunit with altered intrinsic and extrinsic apoptosis and a Perrault syndrome-spectrum phenotype

This study identifies biallelic DAP3 variants causing mitoribosomal dysfunction, leading to combined oxidative phosphorylation deficiency and Perrault syndrome-like features.

Structural variant calling and clinical interpretation in 6224 unsolved rare disease exomes

This study identifies structural variants in 6224 rare disease exomes, finding 0.4% diagnostic yield with 8 previously undetected pathogenic SVs.

Analysis of higher order interactions quantifies co-ordination in the epigenome and reveals novel biological relationships in Kabuki syndrome

The paper quantifies higher order interactions in DNA methylation data from Kabuki syndrome patients and controls, revealing reduced epigenome complexity and novel biological relationships.

Heterozygous loss-of-function SMC3 variants are associated with variable and incompletely penetrant growth and developmental features

The paper identifies SMC3 loss-of-function variants associated with variable growth and developmental features, including some unexpected phenotypes like bone marrow failure and leukemia.

Systematic identification of disease-causing promoter and untranslated region variants in 8,040 undiagnosed individuals with rare disease

This study identifies disease-causing promoter and untranslated region variants in 8,040 undiagnosed rare disease patients using a new framework and finds 12 variants with potential pathogenicity.

A SYSTEMATIC RE-ANALYSIS OF COPY NUMBER LOSSES OF UNCERTAIN CLINICAL SIGNIFICANCE

The paper re-analyzes clinical aCGH data to identify pathogenic copy number losses, finding that 7.2% of class 3 variants were reclassified as pathogenic or likely pathogenic.

Germline intergenic duplications at Xq26.1 underlie Bazex-Dupre-Christol syndrome, an inherited basal cell carcinoma susceptibility condition

The paper identifies intergenic duplications at Xq26.1 as the genetic cause of Bazex-Dupre-Christol syndrome, linking them to ARHGAP36 dysregulation and BCC susceptibility.

Gain and loss of function variants in EZH1 disrupt neurogenesis timing and cause overlapping neurodevelopmental disorders

Critical role of PCYT2 in muscle health and aging

This study identifies PCYT2 as critical for muscle health and aging, showing its deficiency causes muscle weakness and aging, and demonstrates therapeutic potential through AAV-based delivery.

Delineating the molecular and phenotypic spectrum of the SETD1B-related syndrome

The paper characterizes the clinical and molecular features of 36 individuals with SETD1B variants, identifying a core phenotype of developmental delay and variable epilepsy, with male predominance and potential sex-linked effects.

Non-coding variants upstream of MEF2C cause severe developmental disorder through three distinct loss-of-function mechanisms

The paper identifies non-coding variants upstream of MEF2C causing severe developmental disorder through three distinct loss-of-function mechanisms, showing their diagnostic importance in existing exome datasets.

Genotype-phenotype correlations and novel molecular insights into the DHX30-associated neurodevelopmental disorders

This study identifies 25 individuals with DHX30 mutations, showing two clinical subtypes based on variant type and severity of developmental and neurological symptoms.

KMT2D haploinsufficiency in Kabuki Syndrome disrupts neuronal function through transcriptional and chromatin rewiring independent of H3K4-monomethylation

This study investigates how KMT2D mutations in Kabuki Syndrome disrupt neuronal function through chromatin and transcriptional changes, independent of H3K4me1.

Bayesian inference associates rare KDR variants with specific phenotypes in pulmonary arterial hypertension

Whole-genome sequencing of rare disease patients in a national healthcare system

This study uses whole-genome sequencing in a national healthcare system to diagnose rare diseases and discover new aetiological variants, identifying 95 Mendelian associations and 4 novel non-coding disease-causing variants.