VCV002504572.2 - ClinVar

NM_014849.5(SV2A):c.865C>T (p.Arg289Ter)

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.

(2)

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.

Likely pathogenic

criteria provided, single submitter

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_014849.5(SV2A):c.865C>T (p.Arg289Ter)

Variation ID: 2504572 Accession: VCV002504572.2

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 1q21.2 1: 149910916 (GRCh38) [ NCBI UCSC ] 1: 149882468 (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	Dec 2, 2023	Jun 23, 2024	Jun 12, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_014849.5:c.865C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_055664.3:p.Arg289Ter	nonsense
NM_001328674.2:c.865C>T	NP_001315603.1:p.Arg289Ter	nonsense
NM_001328675.2:c.865C>T	NP_001315604.1:p.Arg289Ter	nonsense
NC_000001.11:g.149910916G>A
NC_000001.10:g.149882468G>A
NG_050966.1:g.11967C>T
NG_092102.1:g.338G>A

... more HGVS ... less HGVS

Protein change

R289*

Other names

Canonical SPDI

NC_000001.11:149910915:G: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: 185860.0002 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.
SV2A		-	-	GRCh38 GRCh37	57	69

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.
See cases	Likely pathogenic (1)	criteria provided, single submitter	Jun 12, 2024	RCV003444158.2
Developmental and epileptic encephalopathy 113	Pathogenic (1)	no assertion criteria provided	Mar 25, 2024	RCV003988101.1

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.
Likely pathogenic (Jun 12, 2024)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	see cases (Autosomal recessive inheritance) Affected status: yes Allele origin: biparental	Department Of Genetics, Sultan Qaboos University Hospital, Sultan Qaboos University Accession: SCV003926643.2 First in ClinVar: Dec 02, 2023 Last updated: Jun 23, 2024	Clinical Features: Seizure (present) , Severe global developmental delay (present) Age: 0-9 years Sex: male Ethnicity/Population group: Omani Geographic origin: Oman
Pathogenic (Mar 25, 2024)	no assertion criteria provided Method: literature only	DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY 113 Affected status: not provided Allele origin: germline	OMIM Accession: SCV004803184.1 First in ClinVar: Mar 30, 2024 Last updated: Mar 30, 2024	Publications: PubMed (1) PubMed: 37985816 Comment on evidence: In a 5-year-old boy, born to consanguineous parents, with developmental and epileptic encephalopathy-113 (DEE113; 620772), Al-Maawali et al. (2024) identified homozygosity for a c.865C-T transition … (more) In a 5-year-old boy, born to consanguineous parents, with developmental and epileptic encephalopathy-113 (DEE113; 620772), Al-Maawali et al. (2024) identified homozygosity for a c.865C-T transition (c.865C-T, NM_014849.5) in the SV2A gene, resulting in an arg289-to-ter (R289X) substitution. The mutation, which was identified by whole-exome sequencing and confirmed by Sanger sequencing, was present in the carrier state in the parents. The variant was present in the gnomAD database (v2.1.1) at an allele frequency of 0.000003977 and was not present in gnomAD-v3.1.2. (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 variants in the synaptic vesicle glycoprotein 2 A are associated with epileptic encephalopathy.	Al-Maawali A	European journal of human genetics : EJHG	2024	PMID: 37985816

Text-mined citations for this variant ...

Record last updated Jun 23, 2024

ClinVar Genomic variation as it relates to human health

NM_014849.5(SV2A):c.865C>T (p.Arg289Ter)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...