VCV003068742.13 - ClinVar

NR_003137.3(RNU4-2):n.64_65insT

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(9)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Pathogenic

criteria provided, multiple submitters, no conflicts

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NR_003137.3(RNU4-2):n.64_65insT

Variation ID: 3068742 Accession: VCV003068742.13

Type and length

Insertion, 1 bp

Location

Cytogenetic: 12q24.23 12: 120291839-120291840 (GRCh38) [ NCBI UCSC ] 12: 120729642-120729643 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Apr 15, 2024	Dec 22, 2024	Nov 12, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NR_003137.3:n.64_65insT MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.		non-coding transcript variant
NC_000012.12:g.120291839_120291840insA
NC_000012.11:g.120729642_120729643insA
NG_079835.3:g.2027_2028insA

Protein change

Other names

Canonical SPDI

NC_000012.12:120291839::A

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

Allele frequency Help The frequency of the allele represented by this VCV record.

Links

OMIM: 620823.0001 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
RNU4-1		-	-	GRCh38	-	7
RNU4-2		-	-	GRCh38	-	11
SIRT4		-	-	GRCh38 GRCh37	28	48

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
RNU4-2-associated neurodevelopmental disorder	Pathogenic (1)	criteria provided, single submitter	Apr 10, 2024	RCV003994802.1
not provided	Pathogenic (1)	criteria provided, single submitter	Sep 1, 2024	RCV004573450.6
Neurodevelopmental disorder with hypotonia, brain anomalies, distinctive facies, and absent language	Pathogenic (6)	criteria provided, multiple submitters, no conflicts	Nov 12, 2024	RCV004596615.7
RNU4-2-related condition	Pathogenic (1)	no assertion criteria provided	May 31, 2024	RCV004759364.1

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Pathogenic (Apr 10, 2024)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: literature only	RNU4-2-associated neurodevelopmental disorder (Autosomal dominant inheritance) Affected status: yes Allele origin: de novo	Institute of Human Genetics, University of Leipzig Medical Center Accession: SCV004812940.1 First in ClinVar: Apr 15, 2024 Last updated: Apr 15, 2024	Publications: DOI: 10.1101/2024.04.07.24305438 DOI: 10.1101/2024.04.07.24305438 Comment: This variant was identified as de novo (maternity and paternity confirmed). Criteria applied: PS2_VSTR, PS4_VSTR Number of individuals with the variant: 92 Clinical Features: Seizure (present) , Global developmental delay (present) , Intellectual disability (present) , Microcephaly (present)
Pathogenic (May 03, 2024)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: research	Neurodevelopmental disorder with hypotonia, brain anomalies, distinctive facies, and absent language Affected status: yes Allele origin: de novo	HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology Study: CSER-HudsonAlpha Accession: SCV005093833.1 First in ClinVar: Aug 11, 2024 Last updated: Aug 11, 2024	Number of individuals with the variant: 1 Clinical Features: Micrognathia (present) , Osteopetrosis (present) , Failure to thrive (present) , Short stature (present) , Hypoplasia of the corpus callosum (present) , Delayed speech and … (more) Micrognathia (present) , Osteopetrosis (present) , Failure to thrive (present) , Short stature (present) , Hypoplasia of the corpus callosum (present) , Delayed speech and language development (present) , Seizure (present) , Abnormal facial shape (present) , Hypotonia (present) , Intellectual disability (present) , Microcephaly (present) (less)
Pathogenic (May 21, 2024)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Neurodevelopmental disorder with hypotonia, brain anomalies, distinctive facies, and absent language (Autosomal dominant inheritance) Affected status: yes Allele origin: de novo	Institute of Human Genetics, University of Leipzig Medical Center Accession: SCV005368510.1 First in ClinVar: Oct 13, 2024 Last updated: Oct 13, 2024	Comment: Criteria applied: PM2_MOD,PS2_VSTR,PS4_STR Clinical Features: Global developmental delay (present) , Microcephaly (present) , Global brain atrophy (present) Sex: male
Pathogenic (Oct 23, 2024)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Neurodevelopmental disorder with hypotonia, brain anomalies, distinctive facies, and absent language (Autosomal dominant inheritance) Affected status: yes Allele origin: germline	Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen Accession: SCV005380239.1 First in ClinVar: Oct 26, 2024 Last updated: Oct 26, 2024	Clinical Features: Microcephaly (present) , Global developmental delay (present) , Craniosynostosis syndrome (present)
Pathogenic (Oct 10, 2024)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Neurodevelopmental disorder with hypotonia, brain anomalies, distinctive facies, and absent language (Autosomal dominant inheritance) Affected status: yes Allele origin: germline	Victorian Clinical Genetics Services, Murdoch Childrens Research Institute Additional submitter: Shariant Australia, Australian Genomics Accession: SCV005400526.1 First in ClinVar: Nov 24, 2024 Last updated: Nov 24, 2024	Publications: PubMed (1) PubMed: 38991538 Comment: Based on the classification scheme VCGS_Germline_v1.3.5, this variant is classified as Pathogenic. Following criteria are met: 0105 - The mechanism of disease for this gene … (more) Based on the classification scheme VCGS_Germline_v1.3.5, this variant is classified as Pathogenic. Following criteria are met: 0105 - The mechanism of disease for this gene is not clearly established. (I) 0107 - This gene is associated with autosomal dominant disease. (I) 0217 - Non-coding variant with known effect. Systemic disruption to to 5' splice site usage was observed in RNA-sequencing data from five individuals with RNU4-2 variants, three of whom harboured the n.64_65insT variant (PMID: 38991538). (SP) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (v2, v3 and v4). (SP) 0600 - Variant is located in the defined critical and highly constrained 18bp region in RNU4-2 (PMID: 38991538). (I) 0801 - This variant has strong previous evidence of pathogenicity in unrelated individuals. This is a recurrent pathogenic de novo variant that has been observed in individuals with neurodevelopmental syndrome (PMID: 38991538). (SP) 1203 - This variant has been shown to be de novo in the proband (parental status confirmed) (by trio analysis). (SP) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign (less)
Pathogenic (Nov 12, 2024)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Neurodevelopmental disorder with hypotonia, brain anomalies, distinctive facies, and absent language Affected status: yes Allele origin: de novo, unknown	Undiagnosed Diseases Network, NIH Study: Undiagnosed Diseases Network (UDN) Accession: SCV005421009.1 First in ClinVar: Dec 14, 2024 Last updated: Dec 14, 2024	Publications: PubMed (1) PubMed: 38991538 Comment: See PMID: 38991538. Observation 1: Clinical Features: Narrow forehead (present) , Micrognathia (present) , Esotropia (present) , Hypotelorism (present) , Osteopenia (present) , Global developmental delay (present) , Abnormal corpus callosum morphology … (more) Narrow forehead (present) , Micrognathia (present) , Esotropia (present) , Hypotelorism (present) , Osteopenia (present) , Global developmental delay (present) , Abnormal corpus callosum morphology (present) , Joint hypermobility (present) , Developmental dysplasia of the hip (present) , Bicuspid aortic valve (present) , Hypoplasia of the corpus callosum (present) , Ventriculomegaly (present) , Abnormal sella turcica morphology (present) , Short stature (present) , Decreased body weight (present) , Irregularity of vertebral bodies (present) , Periventricular leukomalacia (present) , Inferior cerebellar vermis hypoplasia (present) , Axial hypotonia (present) , Localized hirsutism (present) , High myopia (present) , Primary microcephaly (present) , Punctate periventricular T2 hyperintense foci (present) (less) Zygosity: Single Heterozygote Age: 10-19 years Sex: female Observation 2: Clinical Features: Hypoplastic labia majora (present) , Abnormality of the dentition (present) , Brachycephaly (present) , Microcephaly (present) , Long face (present) , Microretrognathia (present) , Protruding … (more) Hypoplastic labia majora (present) , Abnormality of the dentition (present) , Brachycephaly (present) , Microcephaly (present) , Long face (present) , Microretrognathia (present) , Protruding ear (present) , Prominent nose (present) , Thick eyebrow (present) , Autism (present) , Absent speech (present) , Umbilical hernia (present) , Atrial septal defect (present) , Myopathic facies (present) , Polymicrogyria (present) , Curly hair (present) , Abnormality of neuronal migration (present) , Intellectual disability, moderate (present) , Supernumerary nipple (present) , Atrial flutter (present) , Premature eruption of permanent teeth (present) , Self-biting (present) (less) Zygosity: Single Heterozygote Age: 10-19 years Sex: female Observation 3: Clinical Features: Urinary retention (present) , Menorrhagia (present) , Microcephaly (present) , Retrognathia (present) , Micrognathia (present) , Macrotia (present) , Strabismus (present) , Downslanted palpebral fissures … (more) Urinary retention (present) , Menorrhagia (present) , Microcephaly (present) , Retrognathia (present) , Micrognathia (present) , Macrotia (present) , Strabismus (present) , Downslanted palpebral fissures (present) , Nystagmus (present) , Motor stereotypies (present) , Abnormal palmar dermatoglyphics (present) , Thickened skin (present) , Brachydactyly (present) , Global developmental delay (present) , Absent speech (present) , Small nail (present) , Hypoplastic toenails (present) , Sandal gap (present) , Pancytopenia (present) , Iron deficiency anemia (present) , Gait ataxia (present) , Broad-based gait (present) , EEG abnormality (present) , Developmental regression (present) , Ileus (present) , Deep venous thrombosis (present) , High, narrow palate (present) , Increased circulating ferritin concentration (present) , Abnormal muscle tone (present) , Short stature (present) , Gastric polyposis (present) , Lateral ventricle dilatation (present) , Abnormal dermatoglyphics (present) , Underfolded superior helices (present) , Congenital bilateral hip dislocation (present) , Intellectual disability, severe (present) , Chronic constipation (present) , Barrett esophagus (present) , Insomnia (present) (less) Zygosity: Single Heterozygote Age: 40-49 years Sex: female Observation 4: Clinical Features: Open mouth (present) , Progressive microcephaly (present) , Acute sinusitis (present) , Malar flattening (present) , Long face (present) , Coarse facial features (present) , … (more) Open mouth (present) , Progressive microcephaly (present) , Acute sinusitis (present) , Malar flattening (present) , Long face (present) , Coarse facial features (present) , Micrognathia (present) , Bulbous nose (present) , Astigmatism (present) , Myopia (present) , Optic nerve hypoplasia (present) , Osteopenia (present) , Anhidrosis (present) , Thumbs, congenital Clasped (present) , Intellectual disability, mild (present) , Global developmental delay (present) , Generalized hypotonia (present) , Abnormal cerebellum morphology (present) , Cerebral hemorrhage (present) , Absent speech (present) , Joint hypermobility (present) , Hepatic steatosis (present) , Failure to thrive (present) , Abnormality of the cardiovascular system (present) , Pes planus (present) , Short foot (present) , Poor suck (present) , Cerebral atrophy (present) , Hypoplasia of the corpus callosum (present) , Ventriculomegaly (present) , Abnormal basal ganglia morphology (present) , Delayed CNS myelination (present) , Recurrent respiratory infections (present) , Exaggerated cupid's bow (present) , Drooling (present) , Sleep abnormality (present) , Hypoplasia of the brainstem (present) , Febrile seizure (within the age range of 3 months to 6 years) (present) , Small cerebral cortex (present) , Abnormal cerebral white matter morphology (present) , Coxa valga (present) , High, narrow palate (present) , Tracheobronchomalacia (present) , Recurrent upper respiratory tract infections (present) , Methylmalonic acidemia (present) , Elevated circulating thyroid-stimulating hormone concentration (present) , Hypercholesterolemia (present) , Abnormality of peripheral nerve conduction (present) , Generalized hypotonia due to defect at the neuromuscular junction (present) , EMG abnormality (present) , Mild short stature (present) , Decreased body weight (present) , Transient hypogammaglobulinemia of infancy (present) , Secondary microcephaly (present) , Elevated circulating alpha-fetoprotein concentration (present) , Severe expressive language delay (present) , Reduced visual acuity (present) , Gaze-evoked horizontal nystagmus (present) , Bilateral conductive hearing impairment (present) , Hypoplastic superior helix (present) , Postnatal growth retardation (present) , Axial hypotonia (present) , Infantile muscular hypotonia (present) , Abnormal thalamus morphology (present) , Delayed fine motor development (present) , Hyperlipoproteinemia (present) , Severe receptive language delay (present) , Functional abnormality of the middle ear (present) , Abnormal skeletal morphology (present) , Abnormal hypothalamus morphology (present) , Appendicular hypotonia (present) , Decreased transferrin saturation (present) , Small pituitary gland (present) , Abnormality of the pineal gland (present) , Widened cerebral subarachnoid space (present) , Abnormal optic chiasm morphology (present) , Delayed ability to stand (present) , Hip subluxation (present) , Oral motor hypotonia (present) , Decreased serum insulin-like growth factor 1 (present) , Decreased circulating iron concentration (present) , Decreased body mass index (present) (less) Zygosity: Single Heterozygote Age: 0-9 years Sex: male Observation 5: Clinical Features: Inguinal hernia (present) , Full cheeks (present) , Posteriorly rotated ears (present) , Prominent nasal bridge (present) , Esotropia (present) , Hyperpigmentation of the skin … (more) Inguinal hernia (present) , Full cheeks (present) , Posteriorly rotated ears (present) , Prominent nasal bridge (present) , Esotropia (present) , Hyperpigmentation of the skin (present) , Cutis marmorata (present) , Seizure (present) , Hypotonia (present) , Global developmental delay (present) , Dandy-Walker malformation (present) , Absent speech (present) , Developmental dysplasia of the hip (present) , Hypoplasia of the corpus callosum (present) , Status epilepticus (present) , Horner syndrome (present) , Drooling (present) , Myotonia with warm-up phenomenon (present) , Short stature (present) , Spontaneous neonatal pneumothorax (present) , Aplasia/Hypoplasia of the cerebellar vermis (present) , Retrocerebellar cyst (present) , Few cafe-au-lait spots (present) , Abnormality of blood circulation (present) , Unilateral cryptorchidism (present) , Sleep abnormality (present) , Raynaud phenomenon (present) , Impaired pain sensation (present) , Gait disturbance (present) (less) Zygosity: Single Heterozygote Age: 10-19 years Sex: male Observation 6: Clinical Features: High palate (present) , Micrognathia (present) , Macrotia (present) , Autism (present) , Seizure (present) , Global developmental delay (present) , Generalized hypotonia (present) , … (more) High palate (present) , Micrognathia (present) , Macrotia (present) , Autism (present) , Seizure (present) , Global developmental delay (present) , Generalized hypotonia (present) , Absent speech (present) , Bilateral ptosis (present) , Hypoplasia of the corpus callosum (present) , EEG abnormality (present) , Abnormal periventricular white matter morphology (present) , Prominent metopic ridge (present) , Lateral ventricle dilatation (present) , Cafe au lait spots, multiple (present) , Hooded upper eyelid (present) , Raynaud phenomenon (present) (less) Zygosity: Single Heterozygote Age: 10-19 years Sex: male Observation 7: Clinical Features: High palate (present) , Microcephaly (present) , Facial asymmetry (present) , Visual impairment (present) , Blue sclerae (present) , Optic nerve hypoplasia (present) , Autistic … (more) High palate (present) , Microcephaly (present) , Facial asymmetry (present) , Visual impairment (present) , Blue sclerae (present) , Optic nerve hypoplasia (present) , Autistic behavior (present) , Hypothyroidism (present) , Decreased response to growth hormone stimulation test (present) , Single transverse palmar crease (present) , Intellectual disability (present) , Global developmental delay (present) , Generalized hypotonia (present) , Developmental dysplasia of the hip (present) , Hypoplasia of the corpus callosum (present) , Wide intermamillary distance (present) , Periventricular nodular heterotopia (present) , Myoclonic seizure (present) , Folate deficiency in CSF (present) (less) Zygosity: Single Heterozygote Age: 10-19 years Sex: male
Pathogenic (Sep 01, 2024)	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2) Method: clinical testing	not provided Affected status: yes Allele origin: germline	CeGaT Center for Human Genetics Tuebingen Accession: SCV005050620.6 First in ClinVar: Jun 17, 2024 Last updated: Dec 22, 2024	Comment: RNU4-2: PS2:Very Strong, PM2, PS4:Moderate Number of individuals with the variant: 4
Pathogenic (Sep 03, 2024)	no assertion criteria provided Method: literature only	ReNU SYNDROME Affected status: not provided Allele origin: germline	OMIM Accession: SCV005077825.2 First in ClinVar: Jul 15, 2024 Last updated: Sep 08, 2024	Publications: PubMed (3) PubMed: 38821540‚ 38859706‚ 38991538 Comment on evidence: In 33 unrelated individuals with ReNU syndrome (RENU; 620851), Greene et al. (2024) identified a de novo heterozygous 1-bp insertion (n.64_65insT, NR_003137.2) in the RNU4-2 … (more) In 33 unrelated individuals with ReNU syndrome (RENU; 620851), Greene et al. (2024) identified a de novo heterozygous 1-bp insertion (n.64_65insT, NR_003137.2) in the RNU4-2 gene. The mutation, which was found by whole-genome sequencing, was not present in the gnomAD database. The G at position 64 of the gene localizes to the U4 snRNA quasi-pseudoknot that is thought to contribute to the stability of the ACAGAGA loop of U6 snRNA (see 180692), which binds 5-prime splice sites and induces splicing after U4-U6 unwinding. Functional studies of the variant and studies of patient cells were not performed, but the authors suggested that the variant could disrupt splicing. In a 5.4-year-old girl, born of unrelated Dutch parents, with RENU, Schot et al. (2024) identified a de novo heterozygous n.64_65insT mutation in the RNU4-2 gene. The variant was not present in 76,215 genomes in gnomAD (v4.0). RNA-seq analysis of patient-derived fibroblasts did not show signs of large-scale intron retention. Additional functional studies were not performed. The patient was part of a cohort of 164 individuals with neurodevelopmental abnormalities who underwent whole-genome sequencing (0.61%). In 89 individuals with RENU, Chen et al. (2024) identified a heterozygous n.64insT mutation in the RUN4-2 gene. The mutation occurred de novo in all individuals from whom parental DNA was available. Moreover, the mutation occurred on the maternal allele in all 54 patients for whom the parental allele of origin could be determined. The mutation was not present in gnomAD (v4.0). RNA-seq analysis of blood samples from 3 individuals with this mutation contained more abnormal splicing events compared to 378 controls, but the difference did not reach significance. However, abnormal splicing events corresponding to increased use of unannotated 5-prime splice sites was significantly increased in mutation carriers compared to controls. Sequence motif analysis showed that the 5-prime splice site positions occurred in the region that pairs directly with the U6 ACAGAGA region during spliceosome activation. (less)
Pathogenic (May 31, 2024)	no assertion criteria provided Method: clinical testing	RNU4-2-related condition Affected status: yes Allele origin: unknown	Undiagnosed Diseases Network, NIH Study: Undiagnosed Diseases Network (NIH), UDN Accession: SCV005368748.1 First in ClinVar: Oct 13, 2024 Last updated: Oct 13, 2024	Publications: PubMed (1) PubMed: 38645094 Comment: functional studies, see Chen et al.. Clinical Features: Strabismus (present) , Blindness (present) , Nystagmus (present) , Autism (present) , Seizure (present) , Failure to thrive (present) , Sleep abnormality (present) , Short … (more) Strabismus (present) , Blindness (present) , Nystagmus (present) , Autism (present) , Seizure (present) , Failure to thrive (present) , Sleep abnormality (present) , Short stature (present) , Lower limb asymmetry (present) , Barrett esophagus (present) (less) Age: 20-29 years Sex: male Tissue: Blood

Comment:

Based on the classification scheme VCGS_Germline_v1.3.5, this variant is classified as Pathogenic. Following criteria are met: 0105 - The mechanism of disease for this gene is not clearly established. (I) 0107 - This gene is associated with autosomal dominant disease. (I) 0217 - Non-coding variant with known effect. Systemic disruption to to 5' splice site usage was observed in RNA-sequencing data from five individuals with RNU4-2 variants, three of whom harboured the n.64_65insT variant (PMID: 38991538). (SP) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (v2, v3 and v4). (SP) 0600 - Variant is located in the defined critical and highly constrained 18bp region in RNU4-2 (PMID: 38991538). (I) 0801 - This variant has strong previous evidence of pathogenicity in unrelated individuals. This is a recurrent pathogenic de novo variant that has been observed in individuals with neurodevelopmental syndrome (PMID: 38991538). (SP) 1203 - This variant has been shown to be de novo in the proband (parental status confirmed) (by trio analysis). (SP) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Comment:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
De novo variants in the RNU4-2 snRNA cause a frequent neurodevelopmental syndrome.	Chen Y	Nature	2024	PMID: 38991538
Re-analysis of whole genome sequencing ends a diagnostic odyssey: Case report of an RNU4-2 related neurodevelopmental disorder.	Schot R	Clinical genetics	2024	PMID: 38859706
Mutations in the U4 snRNA gene RNU4-2 cause one of the most prevalent monogenic neurodevelopmental disorders.	Greene D	Nature medicine	2024	PMID: 38821540
De novo variants in the non-coding spliceosomal snRNA gene RNU4-2 are a frequent cause of syndromic neurodevelopmental disorders.	Chen Y	medRxiv : the preprint server for health sciences	2024	DOI: 10.1101/2024.04.07.24305438
De novo variants in the non-coding spliceosomal snRNA gene RNU4-2 are a frequent cause of syndromic neurodevelopmental disorders.	Chen Y	medRxiv : the preprint server for health sciences	2024	PMID: 38645094

Text-mined citations for this variant ...

Record last updated Dec 22, 2024

ClinVar Genomic variation as it relates to human health

NR_003137.3(RNU4-2):n.64_65insT

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...