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 and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
ClinVar Genomic variation as it relates to human health
NM_153638.4(PANK2):c.137A>T (p.Asp46Val)
Germline
Classification
Help
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.
(10)
Help
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.
Benign/Likely benign
10
criteria provided, multiple submitters, no conflicts
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_153638.4(PANK2):c.137A>T (p.Asp46Val)
Variation ID: 425264 Accession: VCV000425264.48
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 20p13 20: 3889237 (GRCh38) [ NCBI UCSC ] 20: 3869884 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
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 8, 2017 Oct 20, 2024 Aug 1, 2024 - HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_001324191.1:c.-905A>T NM_001324192.1:c.137A>T NP_001311121.1:p.Asp46Val missense NM_024960.6:c.-246+333A>T intron variant NM_153638.4:c.137A>T NP_705902.2:p.Asp46Val missense NR_136715.1:n.304A>T NC_000020.11:g.3889237A>T NC_000020.10:g.3869884A>T NG_008131.3:g.5399A>T NG_199762.1:g.66A>T LRG_1016:g.5399A>T LRG_1016t1:c.137A>T LRG_1016p1:p.Asp46Val - Protein change
- D46V
- Other names
- -
- Canonical SPDI
- NC_000020.11:3889236:A:T
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- -
-
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.
-
0.00020 (T)
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
-
1000 Genomes Project 30x 0.00016
1000 Genomes Project 0.00020
Trans-Omics for Precision Medicine (TOPMed) 0.00134
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00154
Exome Aggregation Consortium (ExAC) 0.00300
The Genome Aggregation Database (gnomAD), exomes 0.00317
The Genome Aggregation Database (gnomAD) 0.00346
- Links
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 | ||
|---|---|---|---|---|---|---|
| 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. |
|||
| PANK2 | - | - |
GRCh38 GRCh37 |
482 | 750 | |
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. |
|---|---|---|---|---|
| Benign/Likely benign (7) |
criteria provided, multiple submitters, no conflicts
|
Aug 1, 2024 | RCV000488345.40 | |
| Benign/Likely benign (2) |
criteria provided, multiple submitters, no conflicts
|
Jan 28, 2024 | RCV001081909.20 | |
| Benign (1) |
criteria provided, single submitter
|
Jul 8, 2022 | RCV002282169.8 |
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. |
|
|---|---|---|---|---|---|
|
Likely benign
(Nov 01, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Athena Diagnostics
Accession: SCV000843006.1
First in ClinVar: May 08, 2017 Last updated: May 08, 2017 |
|
|
|
Likely benign
(Jan 12, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Pigmentary pallidal degeneration
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV001298944.1
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 and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. (less)
|
|
|
Benign
(Jul 08, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
germline
|
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV002571044.1
First in ClinVar: Sep 17, 2022 Last updated: Sep 17, 2022 |
Comment:
Variant summary: PANK2 c.137A>T (p.Asp46Val) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign … (more)
Variant summary: PANK2 c.137A>T (p.Asp46Val) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.0032 in 248940 control chromosomes (gnomAD and Klopstock_2005), including 8 homozygotes. The observed variant frequency is approximately 3-fold of the estimated maximal expected allele frequency for a pathogenic variant in PANK2 causing Pantothenate Kinase-Associated Neurodegeneration (0.0011), strongly suggesting that the variant is benign. c.137A>T has been reported in the literature in the compound heterozygous state in an individual with a suspected mitochondrial disorder (e.g. DaRe_2013), but has not been reported in individuals diagnosed with Pantothenate Kinase-Associated Neurodegeneration. Therefore this report does not provide evidence to support an association of the variant with Pantothenate Kinase-Associated Neurodegeneration. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Six submitters have provided clinical-significance assessments for this variant to ClinVar after 2014 and the majority classified the variant as likely benign (n=3) or benign (n=2). Based on the evidence outlined above, the variant was classified as benign. (less)
|
|
|
Benign
(Jul 22, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV001987350.2
First in ClinVar: Nov 06, 2021 Last updated: Mar 04, 2023 |
Comment:
This variant is associated with the following publications: (PMID: 15843062, 24215330, 31540697, 32456086)
|
|
|
Benign
(Jan 28, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Pigmentary pallidal degeneration
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000752220.7
First in ClinVar: May 28, 2018 Last updated: Feb 20, 2024 |
|
|
|
Likely benign
(Aug 01, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
CeGaT Center for Human Genetics Tuebingen
Accession: SCV000575308.32
First in ClinVar: May 08, 2017 Last updated: Oct 20, 2024 |
Comment:
PANK2: BS2
Number of individuals with the variant: 11
|
|
|
Likely benign
(Jun 01, 2017)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
unknown
|
Mayo Clinic Laboratories, Mayo Clinic
Accession: SCV000801278.1
First in ClinVar: May 08, 2017 Last updated: May 08, 2017 |
|
|
|
Likely benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Clinical Genetics, Academic Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV002034500.1 First in ClinVar: Dec 18, 2021 Last updated: Dec 18, 2021 |
|
|
|
Likely benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Genome Diagnostics Laboratory, Amsterdam University Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV002035307.1 First in ClinVar: Dec 18, 2021 Last updated: Dec 18, 2021 |
|
|
|
Likely benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
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: SCV002038098.1 First in ClinVar: Dec 18, 2021 Last updated: Dec 18, 2021 |
|
Comment:
Comment:
Variant summary: PANK2 c.137A>T (p.Asp46Val) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.0032 in 248940 control chromosomes (gnomAD and Klopstock_2005), including 8 homozygotes. The observed variant frequency is approximately 3-fold of the estimated maximal expected allele frequency for a pathogenic variant in PANK2 causing Pantothenate Kinase-Associated Neurodegeneration (0.0011), strongly suggesting that the variant is benign. c.137A>T has been reported in the literature in the compound heterozygous state in an individual with a suspected mitochondrial disorder (e.g. DaRe_2013), but has not been reported in individuals diagnosed with Pantothenate Kinase-Associated Neurodegeneration. Therefore this report does not provide evidence to support an association of the variant with Pantothenate Kinase-Associated Neurodegeneration. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Six submitters have provided clinical-significance assessments for this variant to ClinVar after 2014 and the majority classified the variant as likely benign (n=3) or benign (n=2). Based on the evidence outlined above, the variant was classified as benign.
Comment:
This variant is associated with the following publications: (PMID: 15843062, 24215330, 31540697, 32456086)
Comment:
PANK2: BS2
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. |
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 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 and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Comment:
Variant summary: PANK2 c.137A>T (p.Asp46Val) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.0032 in 248940 control chromosomes (gnomAD and Klopstock_2005), including 8 homozygotes. The observed variant frequency is approximately 3-fold of the estimated maximal expected allele frequency for a pathogenic variant in PANK2 causing Pantothenate Kinase-Associated Neurodegeneration (0.0011), strongly suggesting that the variant is benign. c.137A>T has been reported in the literature in the compound heterozygous state in an individual with a suspected mitochondrial disorder (e.g. DaRe_2013), but has not been reported in individuals diagnosed with Pantothenate Kinase-Associated Neurodegeneration. Therefore this report does not provide evidence to support an association of the variant with Pantothenate Kinase-Associated Neurodegeneration. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Six submitters have provided clinical-significance assessments for this variant to ClinVar after 2014 and the majority classified the variant as likely benign (n=3) or benign (n=2). Based on the evidence outlined above, the variant was classified as benign.
Comment:
This variant is associated with the following publications: (PMID: 15843062, 24215330, 31540697, 32456086)
Comment:
PANK2: BS2
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Expanded phenotype and hippocampal involvement in a novel compound heterozygosity of adult PLA2G6 associated neurodegeneration (PARK14). | Michelis JP | Parkinsonism & related disorders | 2017 | PMID: 28094106 |
| Targeted exome sequencing for mitochondrial disorders reveals high genetic heterogeneity. | DaRe JT | BMC medical genetics | 2013 | PMID: 24215330 |
| Mutations in the pantothenate kinase gene PANK2 are not associated with Parkinson disease. | Klopstock T | Neuroscience letters | 2005 | PMID: 15843062 |
Text-mined citations for rs148036492 ...
HelpThese citations are identified by LitVar using
the rs number, so they may include citations for more than one variant
at this location. Please review the LitVar results carefully for your
variant of interest.
Record last updated Nov 25, 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.