VCV000009517.1 - ClinVar

NM_021728.4(OTX2):c.81del (p.Ser28fs)

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_021728.4(OTX2):c.81del (p.Ser28fs)

Variation ID: 9517 Accession: VCV000009517.1

Type and length

Deletion, 1 bp

Location

Cytogenetic: 14q22.3 14: 56805376 (GRCh38) [ NCBI UCSC ] 14: 57272094 (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 13, 2015	May 13, 2015	Oct 1, 2008

HGVS

Nucleotide	Protein	Molecular consequence
NM_021728.4:c.81del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_068374.1:p.Ser28fs	frameshift
NM_001270523.2:c.81del	NP_001257452.1:p.Ser28fs	frameshift
NM_001270524.2:c.81del	NP_001257453.1:p.Ser28fs	frameshift
NM_001270525.2:c.81del	NP_001257454.1:p.Ser28fs	frameshift
NM_172337.3:c.81del	NP_758840.1:p.Ser28fs	frameshift
NR_073034.2:n.368del		non-coding transcript variant
NR_073036.2:n.292del		non-coding transcript variant
NC_000014.9:g.56805379del
NC_000014.8:g.57272097del
NG_008204.1:g.10091del
LRG_718t1:c.81del	LRG_718p1:p.Ser28fs

... more HGVS ... less HGVS

Protein change

S28fs

Other names

Canonical SPDI

NC_000014.9:56805375:GGGG:GGG

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

ClinGen: CA212920 OMIM: 600037.0003 dbSNP: rs786205874 VarSome

Comment on variant

NCBI staff reviewed the sequence information reported in PubMed 15846561 to determine the location of this allele on the current reference sequence. They call this variant 252delC.

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.
OTX2		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	254	269

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.
Syndromic microphthalmia type 5	Pathogenic (1)	no assertion criteria provided	Oct 1, 2008	RCV000010125.5

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 (Oct 01, 2008)	no assertion criteria provided Method: literature only	MICROPHTHALMIA, SYNDROMIC 5 Affected status: not provided Allele origin: germline	OMIM Accession: SCV000030346.2 First in ClinVar: Apr 04, 2013 Last updated: May 13, 2015	Publications: PubMed (2) PubMed: 15846561‚ 18628516 Comment on evidence: In a female infant with bilateral severe microphthalmia and associated features (MCOPS5; 610125), Ragge et al. (2005) identified heterozygosity for a 1-bp deletion (81delC) in … (more) In a female infant with bilateral severe microphthalmia and associated features (MCOPS5; 610125), Ragge et al. (2005) identified heterozygosity for a 1-bp deletion (81delC) in exon 3 of the OTX2 gene, predicted to result in a termination codon in exon 4. CT scan revealed a thickened septum pellucidum and slightly enlarged lateral ventricles. A fetus, terminated after ultrasound revealed bilateral microphthalmia and agenesis of the corpus callosum, also carried the mutation. The phenotypically normal mother was found to be a gonosomal mosaic carrier of the mutation. Based on numbering from the first residue of initiation codon as +1, the 252delC mutation is renumbered as 81delC, and exon numbering includes the first 2 noncoding exons (Dateki et al., 2008). (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
OTX2 mutation in a patient with anophthalmia, short stature, and partial growth hormone deficiency: functional studies using the IRBP, HESX1, and POU1F1 promoters.	Dateki S	The Journal of clinical endocrinology and metabolism	2008	PMID: 18628516
Heterozygous mutations of OTX2 cause severe ocular malformations.	Ragge NK	American journal of human genetics	2005	PMID: 15846561

Text-mined citations for rs786205874 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Apr 25, 2022

ClinVar Genomic variation as it relates to human health

NM_021728.4(OTX2):c.81del (p.Ser28fs)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs786205874 ...