ClinVar Genomic variation as it relates to human health
NM_003560.4(PLA2G6):c.2070_2072del (p.Val691del)
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_003560.4(PLA2G6):c.2070_2072del (p.Val691del)
Variation ID: 6198 Accession: VCV000006198.20
- Type and length
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Deletion, 3 bp
- Location
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Cytogenetic: 22q13.1 22: 38113617-38113619 (GRCh38) [ NCBI UCSC ] 22: 38509624-38509626 (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 Nov 23, 2014 Apr 6, 2024 Mar 25, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_003560.4:c.2070_2072del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_003551.2:p.Val691del inframe deletion NM_001004426.2:c.1908_1910del NM_001004426.3:c.1908_1910del NP_001004426.1:p.Val637del inframe deletion NM_001199562.3:c.1908_1910del NP_001186491.1:p.Val637del inframe deletion NM_001349864.2:c.2070_2072del NP_001336793.1:p.Val691del inframe deletion NM_001349865.2:c.1908_1910del NP_001336794.1:p.Val637del inframe deletion NM_001349866.2:c.1908_1910del NP_001336795.1:p.Val637del inframe deletion NM_001349867.2:c.1536_1538del NP_001336796.1:p.Val513del inframe deletion NM_001349868.2:c.1392_1394del NP_001336797.1:p.Val465del inframe deletion NM_001349869.2:c.1374_1376del NP_001336798.1:p.Val459del inframe deletion NM_003560.2:c.2070_2072del NC_000022.11:g.38113619_38113621del NC_000022.10:g.38509626_38509628del NG_007094.3:g.106160_106162del NG_033059.2:g.2051_2053del LRG_1015:g.106160_106162del LRG_1015t1:c.2070_2072del LRG_1015p1:p.Val691del - Protein change
- V691del, V465del, V513del, V459del, V637del
- Other names
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- Canonical SPDI
- NC_000022.11:38113616:ACAAC:AC
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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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- Comment on variant
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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PLA2G6 | - | - |
GRCh38 GRCh37 |
1039 | 1070 |
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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Mar 25, 2024 | RCV000006575.9 | |
Pathogenic (1) |
criteria provided, single submitter
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Feb 8, 2013 | RCV000147311.8 | |
Pathogenic (3) |
criteria provided, multiple submitters, no conflicts
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Oct 11, 2022 | RCV000480455.9 | |
Pathogenic (2) |
criteria provided, single submitter
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Mar 1, 2020 | RCV000761526.4 | |
not provided (1) |
no classification provided
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- | RCV001523781.3 |
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
(Feb 08, 2013)
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criteria provided, single submitter
Method: clinical testing
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iron accumulation in brain
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
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Genetic Services Laboratory, University of Chicago
Accession: SCV000194684.1
First in ClinVar: Nov 23, 2014 Last updated: Nov 23, 2014 |
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Pathogenic
(Jun 17, 2016)
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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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Knight Diagnostic Laboratories, Oregon Health and Sciences University
Accession: SCV001449029.1
First in ClinVar: Dec 12, 2020 Last updated: Dec 12, 2020 |
Number of individuals with the variant: 1
Sex: male
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Pathogenic
(Feb 10, 2021)
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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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Revvity Omics, Revvity
Accession: SCV002018844.3
First in ClinVar: Nov 29, 2021 Last updated: Feb 04, 2024 |
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Pathogenic
(Dec 06, 2023)
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criteria provided, single submitter
Method: clinical testing
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Infantile neuroaxonal dystrophy
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV004300019.1
First in ClinVar: Feb 14, 2024 Last updated: Feb 14, 2024 |
Comment:
This variant, c.2070_2072del, results in the deletion of 1 amino acid(s) of the PLA2G6 protein (p.Val691del), but otherwise preserves the integrity of the reading frame. … (more)
This variant, c.2070_2072del, results in the deletion of 1 amino acid(s) of the PLA2G6 protein (p.Val691del), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individuals with infantile neuroaxonal dystrophy and/or neurodegeneration with brain iron accumulation (PMID: 16783378, 17033970). It is commonly reported in individuals of North African ancestry (PMID: 25164370). ClinVar contains an entry for this variant (Variation ID: 6198). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. Experimental studies have shown that this variant affects PLA2G6 function (PMID: 20886109). For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Mar 01, 2020)
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criteria provided, single submitter
Method: clinical testing
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Neurodegeneration with brain iron accumulation 2B
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
biparental
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Institute of Human Genetics, University of Leipzig Medical Center
Accession: SCV001443022.1
First in ClinVar: Nov 14, 2020 Last updated: Nov 14, 2020 |
Comment:
Review of the variants reported in Reuter et al., 2017, PMID: 28097321: PS3,PM2,PM3_Strong
Clinical Features:
profound ID (present) , mental deterioration (present) , joint contractures (present) , cerebral atrophy (present) , cerebellar hypoplasia (present)
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Pathogenic
(Jun 30, 2022)
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criteria provided, single submitter
Method: clinical testing
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Infantile neuroaxonal dystrophy 1
Affected status: unknown
Allele origin:
germline
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Department Of Genetics, Sultan Qaboos University Hospital, Sultan Qaboos University
Accession: SCV002574728.1
First in ClinVar: Sep 24, 2022 Last updated: Sep 24, 2022 |
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Pathogenic
(Oct 11, 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: SCV000566890.5
First in ClinVar: Apr 27, 2017 Last updated: Mar 04, 2023 |
Comment:
In silico analysis supports a deleterious effect on protein structure/function; In-frame deletion of one amino acid in a non-repeat region; Not observed at significant frequency … (more)
In silico analysis supports a deleterious effect on protein structure/function; In-frame deletion of one amino acid in a non-repeat region; Not observed at significant frequency in large population cohorts (gnomAD); Published functional studies demonstrate a damaging effect on phospholipase activity compared to wildtype controls (Engel et al., 2010); This variant is associated with the following publications: (PMID: 20619503, 25164370, 17033970, 28097321, 16783378, 20886109, 34797406, 33101984) (less)
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Pathogenic
(Mar 25, 2024)
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criteria provided, single submitter
Method: clinical testing
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Infantile neuroaxonal dystrophy
Affected status: unknown
Allele origin:
germline
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Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center
Accession: SCV004806073.1
First in ClinVar: Apr 06, 2024 Last updated: Apr 06, 2024 |
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Pathogenic
(Nov 01, 2006)
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no assertion criteria provided
Method: literature only
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NEURODEGENERATION WITH BRAIN IRON ACCUMULATION 2A
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000026758.3
First in ClinVar: Apr 04, 2013 Last updated: Aug 31, 2015 |
Comment on evidence:
In a case of classic infantile neuroaxonal dystrophy (NBIA2A; 256600), Morgan et al. (2006) found a 3-bp deletion in exon 15 of the PLA2G6 gene, … (more)
In a case of classic infantile neuroaxonal dystrophy (NBIA2A; 256600), Morgan et al. (2006) found a 3-bp deletion in exon 15 of the PLA2G6 gene, 2070_2072delTGT, resulting in deletion of val691 from the protein (V691del). The mutation was present in homozygous state, or possibly hemizygous state because of deletion of 1 allele. In a consanguineous Bedouin kindred with cases of infantile neuroaxonal dystrophy in 3 separate sibships and in another kindred with a single affected individual, Khateeb et al. (2006) found the same 3-nucleotide deletion. The mutation was also found in heterozygosity in a single individual among 300 unrelated Bedouin controls. Both affected families and the unrelated carrier had the same haplotype surrounding the mutation. (less)
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Pathogenic
(Dec 30, 2017)
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no assertion criteria provided
Method: curation
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Neurodegeneration with brain iron accumulation 2B
Affected status: yes
Allele origin:
unknown
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Department Of Genetics, Sultan Qaboos University Hospital, Sultan Qaboos University
Accession: SCV000891661.1
First in ClinVar: Mar 24, 2019 Last updated: Mar 24, 2019 |
Geographic origin: Middle East
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not provided
(-)
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no classification provided
Method: literature only
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Neurodegeneration with brain iron accumulation
Affected status: unknown
Allele origin:
germline
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GeneReviews
Accession: SCV001733542.2
First in ClinVar: Jun 15, 2021 Last updated: Oct 01, 2022 |
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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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Infantile and childhood onset PLA2G6-associated neurodegeneration in a large North African cohort. | Romani M | European journal of neurology | 2015 | PMID: 25164370 |
Catalytic function of PLA2G6 is impaired by mutations associated with infantile neuroaxonal dystrophy but not dystonia-parkinsonism. | Engel LA | PloS one | 2010 | PMID: 20886109 |
PLA2G6 mutation underlies infantile neuroaxonal dystrophy. | Khateeb S | American journal of human genetics | 2006 | PMID: 17033970 |
PLA2G6, encoding a phospholipase A2, is mutated in neurodegenerative disorders with high brain iron. | Morgan NV | Nature genetics | 2006 | PMID: 16783378 |
Text-mined citations for rs587784343 ...
HelpRecord last updated Apr 06, 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.
NCBI staff reviewed the sequence information reported in PubMed 16783378 Supplementary Fig. 3 to determine the location of this allele on the current reference sequence.