rs142832849
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Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2
The ENST00000316562.9(PANK2):c.276G>A(p.Arg92=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00707 in 1,575,564 control chromosomes in the GnomAD database, including 78 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0053 ( 18 hom., cov: 33)
Exomes 𝑓: 0.0073 ( 60 hom. )
Consequence
PANK2
ENST00000316562.9 synonymous
ENST00000316562.9 synonymous
Scores
1
1
Clinical Significance
Conservation
PhyloP100: 1.33
Genes affected
PANK2 (HGNC:15894): (pantothenate kinase 2) This gene encodes a protein belonging to the pantothenate kinase family and is the only member of that family to be expressed in mitochondria. Pantothenate kinase is a key regulatory enzyme in the biosynthesis of coenzyme A (CoA) in bacteria and mammalian cells. It catalyzes the first committed step in the universal biosynthetic pathway leading to CoA and is itself subject to regulation through feedback inhibition by acyl CoA species. Mutations in this gene are associated with HARP syndrome and pantothenate kinase-associated neurodegeneration (PKAN), formerly Hallervorden-Spatz syndrome. Alternative splicing, involving the use of alternate first exons, results in multiple transcripts encoding different isoforms. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -19 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.36).
BP6
Variant 20-3889376-G-A is Benign according to our data. Variant chr20-3889376-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 444564.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-3889376-G-A is described in Lovd as [Benign]. Variant chr20-3889376-G-A is described in Lovd as [Likely_benign].
BP7
Synonymous conserved (PhyloP=1.33 with no splicing effect.
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00527 (803/152380) while in subpopulation NFE AF= 0.008 (544/68038). AF 95% confidence interval is 0.00744. There are 18 homozygotes in gnomad4. There are 366 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 18 AD,AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PANK2 | NM_001386393.1 | upstream_gene_variant | ENST00000610179.7 | NP_001373322.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PANK2 | ENST00000610179.7 | upstream_gene_variant | 1 | NM_001386393.1 | ENSP00000477429 | P2 |
Frequencies
GnomAD3 genomes AF: 0.00527 AC: 803AN: 152262Hom.: 18 Cov.: 33
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GnomAD3 exomes AF: 0.00352 AC: 631AN: 179352Hom.: 2 AF XY: 0.00330 AC XY: 321AN XY: 97374
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GnomAD4 exome AF: 0.00726 AC: 10334AN: 1423184Hom.: 60 Cov.: 31 AF XY: 0.00691 AC XY: 4869AN XY: 704950
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GnomAD4 genome AF: 0.00527 AC: 803AN: 152380Hom.: 18 Cov.: 33 AF XY: 0.00491 AC XY: 366AN XY: 74516
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:10
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:6
Likely benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Feb 23, 2016 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Aug 01, 2024 | PANK2: BP4, BP7, BS2 - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 11, 2019 | - - |
Likely benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
not specified Benign:2
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Feb 15, 2017 | - - |
Pigmentary pallidal degeneration Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | 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. - |
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 31, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at