ClinVar Genomic variation as it relates to human health
NM_000180.4(GUCY2D):c.2944+1del
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.
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.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000180.4(GUCY2D):c.2944+1del
Variation ID: 98582 Accession: VCV000098582.13
- Type and length
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Deletion, 1 bp
- Location
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Cytogenetic: 17p13.1 17: 8015501 (GRCh38) [ NCBI UCSC ] 17: 7918819 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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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 Feb 20, 2014 Oct 8, 2024 Jul 8, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000180.4:c.2944+1del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
splice donor NM_000180.4:c.2944del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
splice donor NM_000180.3:c.2943delG NM_000180.3:c.2944+1delG NM_000180.3:c.2944del NC_000017.11:g.8015503del NC_000017.10:g.7918821del NG_009092.1:g.17834del - Protein change
- Other names
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- Canonical SPDI
- NC_000017.11:8015500:GGG:GG
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe 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.
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Allele frequency
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The frequency of the allele represented by this VCV record.
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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 | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
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The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
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The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
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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. |
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GUCY2D | - | - |
GRCh38 GRCh37 |
1435 | 1470 |
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
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Pathogenic (2) |
criteria provided, single submitter
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May 20, 2022 | RCV000084877.2 | |
Likely pathogenic (4) |
criteria provided, single submitter
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Apr 8, 2021 | RCV001250850.4 | |
Pathogenic (1) |
criteria provided, single submitter
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Jul 8, 2023 | RCV001381496.7 | |
GUCY2D-related disorder
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Pathogenic (1) |
no assertion criteria provided
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Sep 18, 2024 | RCV004748576.1 |
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
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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
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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. |
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Pathogenic
(Jul 08, 2023)
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criteria provided, single submitter
Method: clinical testing
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Leber congenital amaurosis 1
Cone-rod dystrophy 6
Explanation for multiple conditions: Uncertain.
The variant was classified for several related diseases, possibly a spectrum of disease; the variant may be associated with one or more the diseases.
Affected status: unknown
Allele origin:
germline
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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV001579919.4
First in ClinVar: May 10, 2021 Last updated: Feb 28, 2024 |
Comment:
ClinVar contains an entry for this variant (Variation ID: 98582). This sequence change creates a premature translational stop signal (p.Gly982Valfs*39) in the GUCY2D gene. It … (more)
ClinVar contains an entry for this variant (Variation ID: 98582). This sequence change creates a premature translational stop signal (p.Gly982Valfs*39) in the GUCY2D gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in GUCY2D are known to be pathogenic (PMID: 10951519, 11328726). This variant is present in population databases (rs61750185, gnomAD 0.4%), and has an allele count higher than expected for a pathogenic variant. This premature translational stop signal has been observed in individual(s) with autosomal recessive Leber congenital amaurosis (PMID: 12325031). It has also been observed to segregate with disease in related individuals. This variant is also known as c.2944+1del and c.2943delG. For these reasons, this variant has been classified as Pathogenic. (less)
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Likely pathogenic
(Apr 08, 2021)
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criteria provided, single submitter
Method: research
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Leber congenital amaurosis 1
Affected status: yes
Allele origin:
germline
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Ocular Genomics Institute, Massachusetts Eye and Ear
Accession: SCV001573401.1
First in ClinVar: May 10, 2021 Last updated: May 10, 2021 |
Comment:
The GUCY2D c.2944+1del variant was identified in an individual with retinitis pigmentosa with a presumed recessive inheritance pattern. Through a review of available evidence we … (more)
The GUCY2D c.2944+1del variant was identified in an individual with retinitis pigmentosa with a presumed recessive inheritance pattern. Through a review of available evidence we were able to apply the following criteria: PVS1, PM2. Based on this evidence we have classified this variant as Likely Pathogenic. (less)
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Pathogenic
(May 20, 2022)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV002756953.1
First in ClinVar: Dec 03, 2022 Last updated: Dec 03, 2022 |
Comment:
Canonical splice site variant predicted to result in a null allele in a gene for which loss of function is a known mechanism of disease; … (more)
Canonical splice site variant predicted to result in a null allele in a gene for which loss of function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 33109612, 12325031, 29068140, 29559409, 15643614) (less)
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Pathogenic
(Oct 01, 2002)
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no assertion criteria provided
Method: literature only
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LEBER CONGENITAL AMAUROSIS 1
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000030173.1
First in ClinVar: Apr 04, 2013 Last updated: Apr 04, 2013 |
Comment on evidence:
Hanein et al. (2002) identified a homozygous 2943G deletion (2943delG) in the GUCY2D gene in 3 unrelated and nonconsanguineous Leber congenital amaurosis (204000) families of … (more)
Hanein et al. (2002) identified a homozygous 2943G deletion (2943delG) in the GUCY2D gene in 3 unrelated and nonconsanguineous Leber congenital amaurosis (204000) families of Finnish origin, suggesting a founder effect. No linkage disequilibrium was found using polymorphic markers flanking the GUCY2D gene, supporting the view that the mutation is very ancient. Haplotype studies and Bayesian calculation pointed the founder mutation to 150 generations (i.e., 3,000 years ago). (less)
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Pathogenic
(Sep 18, 2024)
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no assertion criteria provided
Method: clinical testing
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GUCY2D-related condition
Affected status: unknown
Allele origin:
germline
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PreventionGenetics, part of Exact Sciences
Accession: SCV005346519.1
First in ClinVar: Oct 08, 2024 Last updated: Oct 08, 2024 |
Comment:
The GUCY2D c.2944+1delG variant is predicted to result in a deletion affecting a canonical splice site. This variant, alternatively referred to as c.2943delG or p.Gly982Valfs*39 … (more)
The GUCY2D c.2944+1delG variant is predicted to result in a deletion affecting a canonical splice site. This variant, alternatively referred to as c.2943delG or p.Gly982Valfs*39 using legacy nomenclature, has been reported in the homozygous and compound heterozygous states in multiple individuals with leber congenital amaurosis (Hanein et al. 2002. PubMed ID: 12325031; Avela et al. 2017. PubMed ID: 29068140), cone-rod dystrophy (Areblom et al. 2023. PubMed ID: 37510321), or other unspecified inherited retinal diseases (Lin et al. 2024. PubMed ID: 38219857). This variant was present in the homozygous state in two related individuals with leber congenital amaurosis (Hanein et al. 2002. PubMed ID: 12325031). This variant is reported in 0.41% of alleles in individuals of European (Finnish) descent in gnomAD. An in vitro experimental study suggests this variant abolishes GUCY2D activity (Peshenko et al. 2020. PubMed ID: 33109612). Variants that disrupt the consensus splice donor site in GUCY2D are expected to be pathogenic. This variant is interpreted as pathogenic. (less)
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Pathogenic
(-)
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no assertion criteria provided
Method: research
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Leber congenital amaurosis 1
Affected status: yes
Allele origin:
inherited
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Laboratory of Genetics in Ophthalmology, Institut Imagine
Accession: SCV001426342.1
First in ClinVar: Aug 02, 2020 Last updated: Aug 02, 2020 |
Number of individuals with the variant: 1
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Pathogenic
(-)
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no assertion criteria provided
Method: research
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Leber congenital amaurosis 1
Affected status: yes
Allele origin:
inherited
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Laboratory of Genetics in Ophthalmology, Institut Imagine
Accession: SCV001426343.1
First in ClinVar: Aug 02, 2020 Last updated: Aug 02, 2020 |
Number of individuals with the variant: 7
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not provided
(-)
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no classification provided
Method: not provided
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not provided
Affected status: not provided
Allele origin:
not provided
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Retina International
Accession: SCV000117013.1
First in ClinVar: Feb 20, 2014 Last updated: Feb 20, 2014
Comment:
http://phencode.bx.psu.edu/cgi-bin/phencode/phencode?build=hg19&id=RISN_GC1:c.2943delG
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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
HelpTitle | Author | Journal | Year | Link |
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Evidence of a founder effect for the RETGC1 (GUCY2D) 2943DelG mutation in Leber congenital amaurosis pedigrees of Finnish origin. | Hanein S | Human mutation | 2002 | PMID: 12325031 |
Complete abolition of the retinal-specific guanylyl cyclase (retGC-1) catalytic ability consistently leads to leber congenital amaurosis (LCA). | Rozet JM | Investigative ophthalmology & visual science | 2001 | PMID: 11328726 |
Spectrum of retGC1 mutations in Leber's congenital amaurosis. | Perrault I | European journal of human genetics : EJHG | 2000 | PMID: 10951519 |
Text-mined citations for rs61750185 ...
HelpRecord last updated Oct 08, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.