ClinVar Genomic variation as it relates to human health
NM_000350.3(ABCA4):c.5917del (p.Gly1972_Val1973insTer)
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_000350.3(ABCA4):c.5917del (p.Gly1972_Val1973insTer)
Variation ID: 99419 Accession: VCV000099419.42
- Type and length
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Deletion, 1 bp
- Location
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Cytogenetic: 1p22.1 1: 94007722 (GRCh38) [ NCBI UCSC ] 1: 94473278 (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 Apr 15, 2024 Dec 2, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000350.3:c.5917del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000341.2:p.Gly1972_Val1973insTer nonsense NM_000350.3:c.5917delG MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
nonsense NM_000350.2:c.5917del NM_001425324.1:c.5695delG NP_001412253.1:p.Val1899Terfs frameshift nonsense NC_000001.11:g.94007722del NC_000001.10:g.94473278del NG_009073.1:g.118428del NG_009073.2:g.118426del - Protein change
- Other names
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- Canonical SPDI
- NC_000001.11:94007721:C:
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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
Help
The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD), exomes 0.00003
Exome Aggregation Consortium (ExAC) 0.00005
The Genome Aggregation Database (gnomAD) 0.00000
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
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. |
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ABCA4 | - | - |
GRCh38 GRCh37 |
3701 | 4056 |
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. |
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Pathogenic (4) |
criteria provided, multiple submitters, no conflicts
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Dec 2, 2023 | RCV000085776.24 | |
Pathogenic (5) |
criteria provided, multiple submitters, no conflicts
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Jan 25, 2023 | RCV000408561.10 | |
Pathogenic (2) |
criteria provided, single submitter
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Dec 22, 2018 | RCV000504777.4 | |
Pathogenic (1) |
no assertion criteria provided
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Sep 1, 2016 | RCV000678514.4 | |
Pathogenic (1) |
no assertion criteria provided
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Jun 23, 2019 | RCV001002810.3 | |
Pathogenic (1) |
no assertion criteria provided
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Sep 3, 2018 | RCV001257850.3 | |
Pathogenic (1) |
criteria provided, single submitter
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- | RCV001542556.4 | |
Pathogenic (1) |
criteria provided, single submitter
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Apr 23, 2019 | RCV001807040.3 | |
Pathogenic (1) |
criteria provided, single submitter
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May 13, 2020 | RCV003985075.1 |
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. |
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Pathogenic
(Jan 01, 2016)
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criteria provided, single submitter
Method: clinical testing
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Severe early-childhood-onset retinal dystrophy
Affected status: yes
Allele origin:
germline
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Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg
Accession: SCV000281942.2
First in ClinVar: Dec 07, 2016 Last updated: Dec 07, 2016 |
Indication for testing: Stargardt disease 1
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Pathogenic
(Dec 22, 2018)
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criteria provided, single submitter
Method: clinical testing
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Retinal dystrophy
Affected status: yes
Allele origin:
germline
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Blueprint Genetics
Accession: SCV001238899.1
First in ClinVar: Apr 18, 2020 Last updated: Apr 18, 2020 |
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Pathogenic
(Oct 23, 2020)
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criteria provided, single submitter
Method: clinical testing
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not provided
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
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Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen
Accession: SCV001446878.1
First in ClinVar: Nov 28, 2020 Last updated: Nov 28, 2020 |
Clinical Features:
Cone-rod dystrophy (present)
Sex: male
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Pathogenic
(-)
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criteria provided, single submitter
Method: clinical testing
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Retinitis pigmentosa 19
Affected status: yes
Allele origin:
germline
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Genomics England Pilot Project, Genomics England
Accession: SCV001760044.1
First in ClinVar: Jul 27, 2021 Last updated: Jul 27, 2021 |
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Pathogenic
(May 31, 2021)
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criteria provided, single submitter
Method: clinical testing
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Severe early-childhood-onset retinal dystrophy
Affected status: yes
Allele origin:
germline
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DBGen Ocular Genomics
Accession: SCV001816100.1
First in ClinVar: Sep 08, 2021 Last updated: Sep 08, 2021 |
Number of individuals with the variant: 1
Sex: male
Ethnicity/Population group: unspecified
Geographic origin: Romania
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Pathogenic
(Apr 23, 2019)
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criteria provided, single submitter
Method: clinical testing
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Cone-rod dystrophy
Affected status: yes
Allele origin:
germline
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Institute of Human Genetics, University Hospital Muenster
Accession: SCV002054120.1
First in ClinVar: Jan 12, 2022 Last updated: Jan 12, 2022 |
Comment:
ACMG categories: PVS1,PM2,PM3,PP4,PP5
Number of individuals with the variant: 1
Age: 20-29 years
Sex: male
Tissue: blood
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Pathogenic
(Dec 03, 2021)
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criteria provided, single submitter
Method: clinical testing
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Severe early-childhood-onset retinal dystrophy
Affected status: yes
Allele origin:
germline
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MGZ Medical Genetics Center
Accession: SCV002579837.1
First in ClinVar: Oct 15, 2022 Last updated: Oct 15, 2022 |
Number of individuals with the variant: 1
Sex: female
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Pathogenic
(Jan 25, 2023)
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criteria provided, single submitter
Method: clinical testing
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Severe early-childhood-onset retinal dystrophy
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
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Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München
Accession: SCV004045888.1
First in ClinVar: Oct 21, 2023 Last updated: Oct 21, 2023 |
Observation 1:
Number of individuals with the variant: 1
Clinical Features:
Visual impairment (present) , Macular atrophy (present)
Observation 2:
Number of individuals with the variant: 1
Clinical Features:
Macular degeneration (present)
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Pathogenic
(Dec 02, 2023)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV001234634.5
First in ClinVar: Apr 15, 2020 Last updated: Feb 14, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Val1973*) in the ABCA4 gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Val1973*) in the ABCA4 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ABCA4 are known to be pathogenic (PMID: 10958761, 24938718, 25312043, 26780318). This variant is present in population databases (rs61751389, gnomAD 0.02%). This premature translational stop signal has been observed in individual(s) with Stargardt disease and inherited retinal disease (PMID: 28041643, 29099798). ClinVar contains an entry for this variant (Variation ID: 99419). For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(May 13, 2020)
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criteria provided, single submitter
Method: clinical testing
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ABCA4-Related Disorders
Affected status: unknown
Allele origin:
unknown
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Illumina Laboratory Services, Illumina
Accession: SCV004801488.1
First in ClinVar: Mar 23, 2024 Last updated: Mar 23, 2024 |
Comment:
The ABCA4 c.5917delG p.(Val1973Ter) nonsense variant is expected to result in the loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. … (more)
The ABCA4 c.5917delG p.(Val1973Ter) nonsense variant is expected to result in the loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. Across a selection of the available literature, the c.5917delG p.(Val1973Ter) variant has been identified in a total of 15 individuals with ABCA4 -related disorders including in nine individuals diagnosed with Stargardt disease, in three of whom the variant was found in a homozygous state, and in six of whom, the variant was found in a compound heterozygous state. Of six individuals diagnosed with cone-rod dystrophy, four carried the variant in a homozygous state, and two in a presumed compound heterozygous state (Rivera et al. 2000; Biggs et al. 2001; Gerth et al. 2002; Riveiro-Alvarez et al. 2013; Schulz et al. 2017; Dockery et al. 2017; Weisschuh et al. 2018). This variant is reported at a frequency of 0.000163 in the South Asian population of the Genome Aggregation Database (version 2.1.1). This allele frequency is consistent with the disease prevalence estimates. Based on the collective evidence the c.5917delG p.(Val1973Ter) variant is classified as pathogenic for ABCA4 -related disorders. (less)
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Pathogenic
(Aug 01, 2019)
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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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CeGaT Center for Human Genetics Tuebingen
Accession: SCV001247600.20
First in ClinVar: May 09, 2020 Last updated: Apr 15, 2024 |
Number of individuals with the variant: 11
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Pathogenic
(Oct 05, 2021)
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criteria provided, single submitter
Method: clinical testing
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Severe early-childhood-onset retinal dystrophy
Affected status: yes
Allele origin:
unknown
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Laboratory of Medical Genetics, National & Kapodistrian University of Athens
Accession: SCV001976839.1
First in ClinVar: Oct 16, 2021 Last updated: Oct 16, 2021 |
Comment:
PVS1, PM2, PP5
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Pathogenic
(Jan 01, 2015)
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no assertion criteria provided
Method: research
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Retinal dystrophy
Affected status: yes
Allele origin:
unknown
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NIHR Bioresource Rare Diseases, University of Cambridge
Accession: SCV000599004.1
First in ClinVar: Sep 09, 2017 Last updated: Sep 09, 2017 |
Number of individuals with the variant: 1
Sex: male
Ethnicity/Population group: European
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Pathogenic
(Jun 23, 2019)
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no assertion criteria provided
Method: research
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Maculopathy
Affected status: yes
Allele origin:
inherited
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Sharon lab, Hadassah-Hebrew University Medical Center
Accession: SCV001160822.1
First in ClinVar: Feb 16, 2020 Last updated: Feb 16, 2020 |
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Pathogenic
(Sep 03, 2018)
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no assertion criteria provided
Method: literature only
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Autosomal recessive Retinitis Pigmentosa
Affected status: yes
Allele origin:
germline
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Faculty of Health Sciences, Beirut Arab University
Accession: SCV001434617.1
First in ClinVar: Oct 03, 2020 Last updated: Oct 03, 2020 |
Number of individuals with the variant: 4
Ethnicity/Population group: Arab
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Pathogenic
(Sep 01, 2016)
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no assertion criteria provided
Method: clinical testing
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Age related macular degeneration 2
Affected status: yes
Allele origin:
inherited
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Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+
Accession: SCV000804585.2
First in ClinVar: Sep 10, 2018 Last updated: Sep 10, 2018 |
Number of individuals with the variant: 1
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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: SCV000117918.1
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_ABCR:c.5917delG
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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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Molecular and clinical analysis of 27 German patients with Leber congenital amaurosis. | Weisschuh N | PloS one | 2018 | PMID: 30576320 |
Mutations in known disease genes account for the majority of autosomal recessive retinal dystrophies. | Patel N | Clinical genetics | 2018 | PMID: 30054919 |
Target 5000: Target Capture Sequencing for Inherited Retinal Degenerations. | Dockery A | Genes | 2017 | PMID: 29099798 |
Mutation Spectrum of the ABCA4 Gene in 335 Stargardt Disease Patients From a Multicenter German Cohort-Impact of Selected Deep Intronic Variants and Common SNPs. | Schulz HL | Investigative ophthalmology & visual science | 2017 | PMID: 28118664 |
Comprehensive Rare Variant Analysis via Whole-Genome Sequencing to Determine the Molecular Pathology of Inherited Retinal Disease. | Carss KJ | American journal of human genetics | 2017 | PMID: 28041643 |
Screening of ABCA4 Gene in a Chinese Cohort With Stargardt Disease or Cone-Rod Dystrophy With a Report on 85 Novel Mutations. | Jiang F | Investigative ophthalmology & visual science | 2016 | PMID: 26780318 |
Clinical and molecular characteristics of childhood-onset Stargardt disease. | Fujinami K | Ophthalmology | 2015 | PMID: 25312043 |
Mutations of 60 known causative genes in 157 families with retinitis pigmentosa based on exome sequencing. | Xu Y | Human genetics | 2014 | PMID: 24938718 |
Outcome of ABCA4 disease-associated alleles in autosomal recessive retinal dystrophies: retrospective analysis in 420 Spanish families. | Riveiro-Alvarez R | Ophthalmology | 2013 | PMID: 23755871 |
A comprehensive survey of sequence variation in the ABCA4 (ABCR) gene in Stargardt disease and age-related macular degeneration. | Rivera A | American journal of human genetics | 2000 | PMID: 10958763 |
Mutations in the ABCA4 (ABCR) gene are the major cause of autosomal recessive cone-rod dystrophy. | Maugeri A | American journal of human genetics | 2000 | PMID: 10958761 |
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Text-mined citations for rs61751389 ...
HelpRecord last updated Apr 20, 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.