VCV003233312.1 - ClinVar

NM_001382637.1(OTUD7A):c.1146del (p.Glu382fs)

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.

(1)

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

no assertion criteria provided

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_001382637.1(OTUD7A):c.1146del (p.Glu382fs)

Variation ID: 3233312 Accession: VCV003233312.1

Type and length

Deletion, 1 bp

Location

Cytogenetic: 15q13.3 15: 31501715 (GRCh38) [ NCBI UCSC ] 15: 31793918 (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	May 1, 2024	May 1, 2024	Apr 25, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_001382637.1:c.1146del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001369566.1:p.Glu382fs	frameshift
NM_001329907.2:c.1146del	NP_001316836.1:p.Glu382fs	frameshift
NM_130901.3:c.1125del	NP_570971.1:p.Glu375fs	frameshift
NC_000015.10:g.31501716del
NC_000015.9:g.31793919del

... more HGVS ... less HGVS

Protein change

E375fs, E382fs

Other names

Canonical SPDI

NC_000015.10:31501714:TT:T

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: 612024.0002 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.
OTUD7A		No evidence available	No evidence available	GRCh38 GRCh38 GRCh38 GRCh37	100	364

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.
Neurodevelopmental disorder with hypotonia and seizures	Pathogenic (1)	no assertion criteria provided	Apr 25, 2024	RCV004525824.1

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 25, 2024)	no assertion criteria provided Method: literature only	NEURODEVELOPMENTAL DISORDER WITH HYPOTONIA AND SEIZURES Affected status: not provided Allele origin: germline	OMIM Accession: SCV005038659.1 First in ClinVar: May 01, 2024 Last updated: May 01, 2024	Publications: PubMed (1) PubMed: 33381903 Comment on evidence: In a 3-year-old boy, born of unrelated parents, with neurodevelopmental disorder with hypotonia and seizures (NEDHS; 620790), Suzuki et al. (2021) identified compound heterozygosity for … (more) In a 3-year-old boy, born of unrelated parents, with neurodevelopmental disorder with hypotonia and seizures (NEDHS; 620790), Suzuki et al. (2021) identified compound heterozygosity for loss of the OTUD7A gene. He had a de novo heterozygous 1-bp deletion (c.1125del, NM_130901.2) in the OTUD7A gene, resulting in a frameshift and premature termination (Glu375AspfsTer11) on 1 allele, and a de novo heterozygous 1.6-Mb deletion of chromosome 15q13.3 (see 612001) that included the OTUD7A gene on the other allele. The point mutation was found by trio-based exome sequencing and confirmed by Sanger sequencing, whereas the deletion was identified through copy number variant analysis. Neither parent carried the mutation or the deletion. Functional studies of the variants and studies of patient cells were not performed, but homozygous expression of the frameshift mutation in the C. elegans homolog resulted in impaired locomotion and disturbed synaptic transmission (see ANIMAL MODEL). (less)

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.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Biallelic loss of OTUD7A causes severe muscular hypotonia, intellectual disability, and seizures.	Suzuki H	American journal of medical genetics. Part A	2021	PMID: 33381903

Text-mined citations for this variant ...

Record last updated Jun 17, 2024

ClinVar Genomic variation as it relates to human health

NM_001382637.1(OTUD7A):c.1146del (p.Glu382fs)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...