ClinVar Genomic variation as it relates to human health
NM_002087.4(GRN):c.99C>T (p.Asp33=)
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_002087.4(GRN):c.99C>T (p.Asp33=)
Variation ID: 98123 Accession: VCV000098123.68
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 17q21.31 17: 44349263 (GRCh38) [ NCBI UCSC ] 17: 42426631 (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 May 12, 2024 Jan 31, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_002087.4:c.99C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_002078.1:p.Asp33= synonymous NC_000017.11:g.44349263C>T NC_000017.10:g.42426631C>T NG_007886.1:g.9141C>T LRG_661:g.9141C>T LRG_661t1:c.99C>T - Protein change
- Other names
- -
- Canonical SPDI
- NC_000017.11:44349262: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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0.00120 (T)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
1000 Genomes Project 0.00120
1000 Genomes Project 30x 0.00172
Trans-Omics for Precision Medicine (TOPMed) 0.00234
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00284
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
Help
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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GRN | - | - |
GRCh38 GRCh37 |
646 | 685 |
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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Likely benign (6) |
criteria provided, multiple submitters, no conflicts
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Jun 1, 2023 | RCV000084425.32 | |
Likely benign (2) |
criteria provided, single submitter
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- | RCV000243797.13 | |
Benign/Likely benign (2) |
criteria provided, multiple submitters, no conflicts
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Jun 20, 2017 | RCV000576806.13 | |
Benign (1) |
criteria provided, single submitter
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Jan 31, 2024 | RCV001080696.15 | |
Likely benign (1) |
criteria provided, single submitter
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Oct 6, 2016 | RCV002313838.9 |
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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Likely benign
(-)
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criteria provided, single submitter
Method: clinical testing
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NOT SPECIFIED
Affected status: unknown
Allele origin:
germline
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PreventionGenetics, part of Exact Sciences
Accession: SCV000308705.1
First in ClinVar: Oct 02, 2016 Last updated: Oct 02, 2016 |
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Benign
(Jun 20, 2017)
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criteria provided, single submitter
Method: clinical testing
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GRN-related frontotemporal lobar degeneration with Tdp43 inclusions
Affected status: unknown
Allele origin:
germline
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Athena Diagnostics
Accession: SCV000677383.1
First in ClinVar: Jan 07, 2018 Last updated: Jan 07, 2018 |
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Likely benign
(Mar 02, 2021)
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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: SCV001792806.1
First in ClinVar: Aug 21, 2021 Last updated: Aug 21, 2021 |
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Likely benign
(Oct 06, 2016)
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criteria provided, single submitter
Method: clinical testing
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Inborn genetic diseases
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV000847821.4
First in ClinVar: Nov 08, 2018 Last updated: May 01, 2024 |
Comment:
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of … (more)
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. (less)
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Likely benign
(Apr 27, 2017)
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criteria provided, single submitter
Method: clinical testing
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GRN-related frontotemporal lobar degeneration with Tdp43 inclusions
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV000403338.3
First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020 |
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more)
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. (less)
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Benign
(Jan 31, 2024)
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criteria provided, single submitter
Method: clinical testing
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Neuronal ceroid lipofuscinosis 11
GRN-related frontotemporal lobar degeneration with Tdp43 inclusions
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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Invitae
Accession: SCV001015743.6
First in ClinVar: Dec 17, 2019 Last updated: Feb 28, 2024 |
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Likely benign
(Jun 01, 2023)
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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: SCV002063623.15
First in ClinVar: Jan 29, 2022 Last updated: May 12, 2024 |
Comment:
GRN: BP4, BP7
Number of individuals with the variant: 10
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Benign
(May 23, 2017)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
unknown
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Mayo Clinic Laboratories, Mayo Clinic
Accession: SCV000801378.1
First in ClinVar: Feb 20, 2014 Last updated: Feb 20, 2014 |
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Likely benign
(-)
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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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Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001964138.1 First in ClinVar: Oct 07, 2021 Last updated: Oct 07, 2021 |
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Benign
(-)
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no assertion criteria provided
Method: clinical testing
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not specified
Affected status: yes
Allele origin:
germline
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Genome Diagnostics Laboratory, Amsterdam University Medical Center
Study: VKGL Data-share Consensus
Accession: SCV001809343.1 First in ClinVar: Aug 25, 2021 Last updated: Aug 25, 2021 |
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Likely benign
(-)
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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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Genome Diagnostics Laboratory, University Medical Center Utrecht
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001927820.1 First in ClinVar: Sep 24, 2021 Last updated: Sep 24, 2021 |
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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:
unknown
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VIB Department of Molecular Genetics, University of Antwerp
Accession: SCV000116561.1
First in ClinVar: Feb 20, 2014 Last updated: Feb 20, 2014
Comment:
http://phencode.bx.psu.edu/cgi-bin/phencode/phencode?build=hg18&id=ADM_299
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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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No major progranulin genetic variability contribution to disease etiopathogenesis in an ALS Italian cohort. | Del Bo R | Neurobiology of aging | 2011 | PMID: 19632744 |
The spectrum of mutations in progranulin: a collaborative study screening 545 cases of neurodegeneration. | Yu CE | Archives of neurology | 2010 | PMID: 20142524 |
A thorough assessment of benign genetic variability in GRN and MAPT. | Guerreiro RJ | Human mutation | 2010 | PMID: 20020531 |
Progranulin mutation causes frontotemporal dementia in the Swedish Karolinska family. | Chiang HH | Alzheimer's & dementia : the journal of the Alzheimer's Association | 2008 | PMID: 19012866 |
Novel exon 1 progranulin gene variant in Alzheimer's disease. | Cortini F | European journal of neurology | 2008 | PMID: 18752597 |
Progranulin genetic variability contributes to amyotrophic lateral sclerosis. | Sleegers K | Neurology | 2008 | PMID: 18184915 |
Molecular characterization of novel progranulin (GRN) mutations in frontotemporal dementia. | Mukherjee O | Human mutation | 2008 | PMID: 18183624 |
Progranulin null mutations in both sporadic and familial frontotemporal dementia. | Le Ber I | Human mutation | 2007 | PMID: 17436289 |
Progranulin mutations and amyotrophic lateral sclerosis or amyotrophic lateral sclerosis-frontotemporal dementia phenotypes. | Schymick JC | Journal of neurology, neurosurgery, and psychiatry | 2007 | PMID: 17371905 |
Mutations other than null mutations producing a pathogenic loss of progranulin in frontotemporal dementia. | van der Zee J | Human mutation | 2007 | PMID: 17345602 |
Mutations in progranulin are a major cause of ubiquitin-positive frontotemporal lobar degeneration. | Gass J | Human molecular genetics | 2006 | PMID: 16950801 |
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Text-mined citations for rs63750742 ...
HelpRecord last updated May 12, 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.