ClinVar Genomic variation as it relates to human health
NM_002016.2(FLG):c.3321del (p.Gly1109fs)
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_002016.2(FLG):c.3321del (p.Gly1109fs)
Variation ID: 420115 Accession: VCV000420115.11
- Type and length
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Deletion, 1 bp
- Location
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Cytogenetic: 1q21.3 1: 152311565 (GRCh38) [ NCBI UCSC ] 1: 152284041 (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 13, 2017 Oct 28, 2023 Apr 11, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_002016.2:c.3321del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_002007.1:p.Gly1109fs frameshift NM_002016.1:c.3321delA NC_000001.11:g.152311565del NC_000001.10:g.152284041del NG_016190.1:g.18639del LRG_1028:g.18639del LRG_1028t1:c.3321del - Protein change
- G1109fs
- Other names
- -
- Canonical SPDI
- NC_000001.11:152311564:T:
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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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0.00140 ()
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00008
The Genome Aggregation Database (gnomAD) 0.00029
Exome Aggregation Consortium (ExAC) 0.00068
Trans-Omics for Precision Medicine (TOPMed) 0.00068
The Genome Aggregation Database (gnomAD), exomes 0.00073
1000 Genomes Project 0.00140
1000 Genomes Project 30x 0.00141
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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FLG | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
2 | 1254 | |
FLG-AS1 | - | - | - | GRCh38 | - | 371 |
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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Apr 11, 2023 | RCV000017718.33 | |
risk factor (1) |
no assertion criteria provided
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Feb 1, 2007 | RCV000017719.3 | |
Pathogenic (3) |
criteria provided, single submitter
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May 24, 2022 | RCV000487070.7 |
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
(May 24, 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: SCV000568701.6
First in ClinVar: Apr 27, 2017 Last updated: Mar 04, 2023 |
Comment:
One of the most common pathogenic variants in the FLG gene reported in individuals of Asian descent with atopic dermatitis and has been described in … (more)
One of the most common pathogenic variants in the FLG gene reported in individuals of Asian descent with atopic dermatitis and has been described in Chinese, Japanese, Korean, and Singaporean populations (Nomura et al., 2007; Meng et al., 2014); Frameshift variant in the C-terminus predicted to result in protein truncation, as the last 2953 amino acids are lost and replaced with 12 incorrect amino acids; This variant is associated with the following publications: (PMID: 21923666, 22407025, 22220561, 23152869, 24858702, 23744309, 17291859, 27519469, 27270549, 18521703, 28120571, 29380403, 30021537, 34426522) (less)
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Pathogenic
(May 04, 2022)
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criteria provided, single submitter
Method: clinical testing
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Ichthyosis vulgaris
Affected status: unknown
Allele origin:
germline
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Mendelics
Accession: SCV002516391.1
First in ClinVar: May 28, 2022 Last updated: May 28, 2022 |
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Pathogenic
(Apr 11, 2023)
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criteria provided, single submitter
Method: clinical testing
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Ichthyosis vulgaris
Affected status: no
Allele origin:
germline
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Genome-Nilou Lab
Accession: SCV004050257.1
First in ClinVar: Oct 28, 2023 Last updated: Oct 28, 2023 |
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risk factor
(Feb 01, 2007)
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no assertion criteria provided
Method: literature only
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DERMATITIS, ATOPIC, 2, SUSCEPTIBILITY TO
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000037996.2
First in ClinVar: Apr 04, 2013 Last updated: Feb 13, 2017 |
Comment on evidence:
In 2 probands from 2 unrelated Japanese families with ichthyosis vulgaris (146700), who were negative for previously identified null mutations in the FLG gene, Nomura … (more)
In 2 probands from 2 unrelated Japanese families with ichthyosis vulgaris (146700), who were negative for previously identified null mutations in the FLG gene, Nomura et al. (2007) identified heterozygosity for a 1-bp deletion (3321delA) in exon 3 of the FLG gene, resulting in a premature termination of profilaggrin translation in filaggrin repeat domain 2. The authors then screened 143 Japanese patients with atopic dermatitis (605803) from 140 unrelated families for this deletion and identified 3321delA in 2 patients. The deletion was not found in 156 unrelated nonatopic and nonichthyotic Japanese controls. (less)
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Pathogenic
(Feb 01, 2007)
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no assertion criteria provided
Method: literature only
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ICHTHYOSIS VULGARIS
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000037995.2
First in ClinVar: Apr 04, 2013 Last updated: Feb 13, 2017 |
Comment on evidence:
In 2 probands from 2 unrelated Japanese families with ichthyosis vulgaris (146700), who were negative for previously identified null mutations in the FLG gene, Nomura … (more)
In 2 probands from 2 unrelated Japanese families with ichthyosis vulgaris (146700), who were negative for previously identified null mutations in the FLG gene, Nomura et al. (2007) identified heterozygosity for a 1-bp deletion (3321delA) in exon 3 of the FLG gene, resulting in a premature termination of profilaggrin translation in filaggrin repeat domain 2. The authors then screened 143 Japanese patients with atopic dermatitis (605803) from 140 unrelated families for this deletion and identified 3321delA in 2 patients. The deletion was not found in 156 unrelated nonatopic and nonichthyotic Japanese controls. (less)
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Pathogenic
(Jan 06, 2020)
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no assertion criteria provided
Method: curation
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Ichthyosis vulgaris
Affected status: unknown
Allele origin:
germline
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Reproductive Health Research and Development, BGI Genomics
Accession: SCV001142308.1
First in ClinVar: Jan 12, 2020 Last updated: Jan 12, 2020 |
Comment:
NM_002016.1:c.3321delA in the FLG gene has an allele frequency of 0.01 in East Asia subpopulation in the gnomAD database.This variant is predicted to cause loss … (more)
NM_002016.1:c.3321delA in the FLG gene has an allele frequency of 0.01 in East Asia subpopulation in the gnomAD database.This variant is predicted to cause loss of normal protein function through protein truncation. The patient's phenotype is highly specific for FLG (PMID: 17291859). Taken together, we interprete this variant as Pathogenic/Likely pathogenic. ACMG/AMP criteria applied: PVS1; PM2_supporting; PP4. (less)
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Pathogenic
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001963084.1 First in ClinVar: Oct 08, 2021 Last updated: Oct 08, 2021 |
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Pathogenic
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001953777.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021 |
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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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Unique mutations in the filaggrin gene in Japanese patients with ichthyosis vulgaris and atopic dermatitis. | Nomura T | The Journal of allergy and clinical immunology | 2007 | PMID: 17291859 |
Text-mined citations for rs200519781 ...
HelpRecord last updated Dec 25, 2023
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.