VCV000013009.1 - ClinVar

NM_002929.3(GRK1):c.1069+3317_1195-753del

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_002929.3(GRK1):c.1069+3317_1195-753del

Variation ID: 13009 Accession: VCV000013009.1

Type and length

Deletion, 5,658 bp

Location

Cytogenetic: 13q34 13: 113726472-113732129 (GRCh38) [ NCBI UCSC ] 13: 114429445-114435102 (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 4, 2013	Apr 4, 2013	Jan 6, 1998

HGVS

Nucleotide	Protein	Molecular consequence
NM_002929.3:c.1069+3317_1195-753del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.		splice acceptor splice donor
NC_000013.11:g.113726474_113732131del
NC_000013.10:g.114429447_114435104del

Protein change

Other names

EX5DEL

Canonical SPDI

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: 180381.0001 VarSome

Comment on variant

NCBI staff provided an HGVS expression for allelic variant 180381.0001 from the sequence of the breakpoint in Figure 1b of the paper by Yamamoto et al., 1997 (PubMed 9020843).

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.
GRK1		-	-	GRCh38 GRCh38 GRCh38	67	141

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.
Oguchi disease-2	Pathogenic (1)	no assertion criteria provided	Jan 6, 1998	RCV000013883.17

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 (Jan 06, 1998)	no assertion criteria provided Method: literature only	OGUCHI DISEASE 2 Affected status: not provided Allele origin: germline	OMIM Accession: SCV000034130.1 First in ClinVar: Apr 04, 2013 Last updated: Apr 04, 2013	Publications: PubMed (2) PubMed: 9020843‚ 9419375 Comment on evidence: In 2 European patients with Oguchi disease-2 (613411), Yamamoto et al. (1997) found homozygosity for a deletion encompassing exon 5 of the GRK1 gene, predicted … (more) In 2 European patients with Oguchi disease-2 (613411), Yamamoto et al. (1997) found homozygosity for a deletion encompassing exon 5 of the GRK1 gene, predicted to lead to a nonfunctional protein. The abnormality was detected by SSCP. The deletion of exon 5 began in intron 4, approximately 2.5 kb downstream of exon 4 and within a region of 8 to 9 tandemly repeated units of 63 bp. Sequence analysis revealed the same breakpoint in 2 patients. Exon 5 contains codons 357-398, encoding amino acid residues within the catalytic domain of rhodopsin kinase. Its deletion from mRNA would lead to the loss of these residues and a predicted frameshift with a premature stop 18 codons downstream. Other family members were heterozygous for the deletion. Although the families of these 2 individuals knew of no relationship between themselves, both had Jewish ancestors who came from northern Hungary or Ukraine. Cideciyan et al. (1998) demonstrated that both homozygotes and heterozygotes with the exon 5 deletion had recovery phase abnormalities of rod-isolated photoresponses by electroretinography (ERG); photoactivation was normal. The investigators concluded that the role of rhodopsin kinase in rods is to accelerate inactivation of activated rhodopsin molecules that, in concert with regeneration, leads to the normal rate of recovery of sensitivity. Cones may rely mainly on regeneration for the inactivation of photolyzed visual pigment, but rhodopsin kinase contributes to cone recovery also. (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
Null mutation in the rhodopsin kinase gene slows recovery kinetics of rod and cone phototransduction in man.	Cideciyan AV	Proceedings of the National Academy of Sciences of the United States of America	1998	PMID: 9419375
Defects in the rhodopsin kinase gene in the Oguchi form of stationary night blindness.	Yamamoto S	Nature genetics	1997	PMID: 9020843

Text-mined citations for this variant ...

Record last updated Aug 11, 2022

ClinVar Genomic variation as it relates to human health

NM_002929.3(GRK1):c.1069+3317_1195-753del

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...