ClinVar Genomic variation as it relates to human health
NM_018062.4(FANCL):c.622G>A (p.Asp208Asn)
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_018062.4(FANCL):c.622G>A (p.Asp208Asn)
Variation ID: 526332 Accession: VCV000526332.11
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 2p16.1 2: 58165793 (GRCh38) [ NCBI UCSC ] 2: 58392928 (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 May 28, 2018 Feb 7, 2023 Oct 11, 2022 - HGVS
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Nucleotide Protein Molecular
consequenceNM_018062.4:c.622G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_060532.2:p.Asp208Asn missense NM_001114636.2:c.637G>A NP_001108108.1:p.Asp213Asn missense NM_001374615.1:c.667G>A NP_001361544.1:p.Asp223Asn missense NM_001410792.1:c.682G>A NP_001397721.1:p.Asp228Asn missense NR_156742.2:n.356G>A NR_164659.2:n.649G>A NC_000002.12:g.58165793C>T NC_000002.11:g.58392928C>T NG_007418.1:g.80587G>A LRG_501:g.80587G>A LRG_501t1:c.637G>A LRG_501p1:p.Asp213Asn LRG_501t2:c.622G>A LRG_501p2:p.Asp208Asn - Protein change
- D208N, D213N, D223N, D228N
- Other names
- -
- Canonical SPDI
- NC_000002.12:58165792:C: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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0.00020 (T)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD) 0.00004
Trans-Omics for Precision Medicine (TOPMed) 0.00007
The Genome Aggregation Database (gnomAD), exomes 0.00011
Exome Aggregation Consortium (ExAC) 0.00012
1000 Genomes Project 30x 0.00016
1000 Genomes Project 0.00020
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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FANCL | - | - |
GRCh38 GRCh37 |
675 | 740 |
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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Uncertain significance (2) |
criteria provided, multiple submitters, no conflicts
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Oct 11, 2022 | RCV000630848.7 | |
Uncertain significance (2) |
criteria provided, multiple submitters, no conflicts
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Aug 6, 2021 | RCV001142205.5 |
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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Uncertain significance
(Jan 12, 2018)
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criteria provided, single submitter
Method: clinical testing
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Fanconi anemia complementation group L
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV001302622.1
First in ClinVar: May 31, 2020 Last updated: May 31, 2020 |
Comment:
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more)
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. (less)
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Uncertain significance
(Oct 11, 2022)
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criteria provided, single submitter
Method: clinical testing
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Fanconi anemia
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000751817.5
First in ClinVar: May 28, 2018 Last updated: Feb 07, 2023 |
Comment:
This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 208 of the FANCL protein … (more)
This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 208 of the FANCL protein (p.Asp208Asn). This variant is present in population databases (rs199564543, gnomAD 0.1%). This missense change has been observed in individual(s) with premature ovarian insufficiency (PMID: 32789750). This variant is also known as c.637G>A (p.Asp213Asn). ClinVar contains an entry for this variant (Variation ID: 526332). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt FANCL protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. (less)
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Uncertain significance
(Feb 09, 2022)
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criteria provided, single submitter
Method: curation
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Fanconi anemia
Affected status: unknown
Allele origin:
germline
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Sema4, Sema4
Accession: SCV002527289.1
First in ClinVar: Jun 24, 2022 Last updated: Jun 24, 2022
Comment:
The FANCL c.622G>A (p.D208N) has been reported in at least one individual with secondary amenorrhea (PMID: 32789750). This variant was observed in 27/251422 chromosomes across … (more)
The FANCL c.622G>A (p.D208N) has been reported in at least one individual with secondary amenorrhea (PMID: 32789750). This variant was observed in 27/251422 chromosomes across all population in the large and broad cohorts in the Genome Aggregation Database (http://gnomad.broadinstitute.org, PMID: 32461654). The variant has been reported in ClinVar (Variation ID: 526332). Functional studies have not been performed, and in silico predictions of the variant's effect on protein function are inconclusive. The evidence is insufficient to meet ACMG/AMP criteria for classifying the variant as benign or pathogenic. Thus, the clinical significance of this variant is currently uncertain. (less)
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Uncertain significance
(Aug 06, 2021)
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criteria provided, single submitter
Method: clinical testing
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Fanconi anemia complementation group L
Affected status: unknown
Allele origin:
unknown
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Fulgent Genetics, Fulgent Genetics
Accession: SCV002782441.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 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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Novel variants in women with premature ovarian function decline identified via whole-exome sequencing. | Tang R | Journal of assisted reproduction and genetics | 2020 | PMID: 32789750 |
Text-mined citations for rs199564543 ...
HelpRecord last updated May 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.