Splicing variant of WDR37 in a case of Neurooculocardiogenitourinary syndrome

Samejima, Mai; Nakashima, Mitsuko; Shibasaki, Jun; Saitsu, Hirotomo; Kato, Mitsuhiro

doi:10.1016/j.braindev.2023.11.007

Cited by 3 publications

(2 citation statements)

References 8 publications

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“…Among these variants, the splicing change in WDR37, CEP290 has been con rmed in the previous reports 10, 24 . Three of four variants have been registered as P or LP in ClinVar, including a WDR37 variant which we registered 10 .…”

Section: Resultsmentioning

confidence: 99%

“…Exome capture and sequencing platform varies these periods: SureSelect Human All Exon V6 Kit (Agilent Technologies, Santa Clara, CA) and NextSeq500 (Illumina, San Diego, CA) paired-end sequencing (93 cases), xGen Exome Research Panel kit (IDT, Coralville IA) capture and NextSeq500 sequencing (87 cases) or DNBseq sequencing (18 cases), and Twist Exome 2.0 capture and NovaSeq600 sequencing (44 cases). Some of these patients have been reported [10][11][12][13][14][15][16][17][18] . The de nition of pathogenic variant was "Pathogenic" or "Likely pathogenic" according to the ACMG/AMP 2015 guideline 19 and previously reported pathogenic variants.…”

Section: Variant Selectionmentioning

confidence: 99%

See 1 more Smart Citation

The impact of variant annotations on the diagnostic yield of exome sequencing for rare pediatric neurological diseases

Komatsu,

Kato,

Kubota

et al. 2024

Preprint

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Variant annotations are crucial for the efficient identification of pathogenic variants. In this study, we retrospectively evaluated the impact of various annotations on identifying 273 pathogenic single nucleotide and small insertion/deletion variants (SNVs/small indels) from 242 patients. Although variant filtering based on allele frequency is essential for narrowing down candidate variants, we found that 13 de novo pathogenic variants in autosomal dominant or X-linked dominant genes had been registered in gnomADv4.0 or 54KJPN with an allele frequency of less than 0.001%, suggesting that very rare variants in large cohort data can be pathogenic de novo variants. Strikingly, 38.1% candidate SNVs/small indels had been registered in the ClinVar database as pathogenic or likely pathogenic, highlighting great utility of this database. SpliceAI can detect candidate variants affecting RNA splicing, leading to the identification of four variants located at 11 to 50-bp away from the exon-intron boundary. Prioritization of candidate genes by patients’ phenotypes using PhenoMatcher module revealed that approximately 95% of the candidate genes had a maximum PhenoMatch score of ≥ 0.6, suggesting the utility of variant prioritization using phenotypes. This study suggests that a combination of multiple annotations and the appropriate evaluation can improve the diagnostic yield of rare diseases.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Variant Selectionmentioning

confidence: 99%

The impact of variant annotations on the diagnostic yield of exome sequencing for rare pediatric neurological diseases

Komatsu,

Kato,

Kubota

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

Congenital anterior segment ocular disorders: Genotype-phenotype correlations and emerging novel mechanisms

Reis,

Seese,

Costakos

et al. 2024

Progress in Retinal and Eye Research

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Identifying pathogenic variants in rare pediatric neurological diseases using exome sequencing

Komatsu,

Kato,

Kubota

et al. 2024

Sci Rep

View full text Add to dashboard Cite

Variant annotations are crucial for efficient identification of pathogenic variants. In this study, we retrospectively analyzed the utility of four annotation tools (allele frequency, ClinVar, SpliceAI, and Phenomatcher) in identifying 271 pathogenic single nucleotide and small insertion/deletion variants (SNVs/small indels). Although variant filtering based on allele frequency is essential for narrowing down on candidate variants, we found that 13 de novo pathogenic variants in autosomal dominant or X-linked dominant genes are registered in gnomADv4.0 or 54KJPN, with an allele frequency of less than 0.001%, suggesting that very rare variants in large cohort data can be pathogenic de novo variants. Notably, 38.4% candidate SNVs/small indels are registered in the ClinVar database as pathogenic or likely pathogenic, which highlights the significance of this database. SpliceAI can detect candidate variants affecting RNA splicing, leading to the identification of four variants located 11 to 50 bp away from the exon–intron boundary. Prioritization of candidate genes by proband phenotype using the PhenoMatcher module revealed that approximately 95% of the candidate genes had a maximum PhenoMatch score ≥ 0.6, suggesting the utility of phenotype-based variant prioritization. Our results suggest that a combination of multiple annotation tools and appropriate evaluation can improve the diagnosis of rare diseases.

show abstract

Splicing variant of WDR37 in a case of Neurooculocardiogenitourinary syndrome

Cited by 3 publications

References 8 publications

The impact of variant annotations on the diagnostic yield of exome sequencing for rare pediatric neurological diseases

The impact of variant annotations on the diagnostic yield of exome sequencing for rare pediatric neurological diseases

Congenital anterior segment ocular disorders: Genotype-phenotype correlations and emerging novel mechanisms

Identifying pathogenic variants in rare pediatric neurological diseases using exome sequencing

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