VCV002584532.1 - ClinVar

NM_021728.4(OTX2):c.497_503dup (p.Ser169fs)

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.

Likely pathogenic

criteria provided, single submitter

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_021728.4(OTX2):c.497_503dup (p.Ser169fs)

Variation ID: 2584532 Accession: VCV002584532.1

Type and length

Duplication, 7 bp

Location

Cytogenetic: 14q22.3 14: 56802125-56802126 (GRCh38) [ NCBI UCSC ] 14: 57268843-57268844 (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	Oct 21, 2023	Oct 21, 2023

HGVS

Nucleotide	Protein	Molecular consequence
NM_021728.4:c.497_503dup MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_068374.1:p.Ser169fs	frameshift
NM_001270523.2:c.473_479dup	NP_001257452.1:p.Ser161fs	frameshift
NM_001270524.2:c.473_479dup	NP_001257453.1:p.Ser161fs	frameshift
NM_001270525.2:c.497_503dup	NP_001257454.1:p.Ser169fs	frameshift
NM_172337.3:c.473_479dup	NP_758840.1:p.Ser161fs	frameshift
NR_073034.2:n.608_614dup		non-coding transcript variant
NR_073036.2:n.532_538dup		non-coding transcript variant
NC_000014.9:g.56802128_56802134dup
NC_000014.8:g.57268846_57268852dup
NG_008204.2:g.19562_19568dup
LRG_718:g.19562_19568dup
LRG_718t1:c.497_503dup	LRG_718p1:p.Ser169fs

... more HGVS ... less HGVS

Protein change

S161fs, S169fs

Other names

Canonical SPDI

NC_000014.9:56802125:AGTGGGGAG:AGTGGGGAGTGGGGAG

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

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.
OTX2		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	253	268

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.
OTX2-related disorder	Likely pathogenic (1)	criteria provided, single submitter	-	RCV004545865.1

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 (-)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	OTX2-related disorders Affected status: yes Allele origin: germline	Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego Accession: SCV004046413.1 First in ClinVar: Oct 21, 2023 Last updated: Oct 21, 2023	Comment: This frameshifting variant in exon 5 of 5 introduces a premature stop codon and is therefore predicted to result in loss of normal protein function … (more) This frameshifting variant in exon 5 of 5 introduces a premature stop codon and is therefore predicted to result in loss of normal protein function through protein truncation. It is absent from the gnomAD population database and thus is presumed to be rare. Based on the available evidence, the c.497_503dup (p.Ser169ProfsTer28) variant is classified as Likely Pathogenic. (less)

Comment:

This frameshifting variant in exon 5 of 5 introduces a premature stop codon and is therefore predicted to result in loss of normal protein function through protein truncation. It is absent from the gnomAD population database and thus is presumed to be rare. Based on the available evidence, the c.497_503dup (p.Ser169ProfsTer28) variant is classified as Likely Pathogenic.

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

There are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar.

Text-mined citations for this variant ...

Record last updated Nov 03, 2024

ClinVar Genomic variation as it relates to human health

NM_021728.4(OTX2):c.497_503dup (p.Ser169fs)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...