20-3889090-G-A

Position:

• chr20-3889090-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000316562.9(PANK2):​c.-11G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00176 in 1,534,030 control chromosomes in the GnomAD database, including 79 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0025 (6 hom., cov: 32)
  • Exomes 𝑓: 0.0017 (73 hom.)
• Consequence: PANK2 ENST00000316562.9 5_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.0990

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]

PANK2-AS1 (HGNC:40732): (PANK2 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP6: Variant 20-3889090-G-A is Benign according to our data. Variant chr20-3889090-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 287783.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0582 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PANK2-AS1	XR_001754478.3	n.84C>T		non_coding_transcript_exon_variant	1/2
PANK2	NM_001324192.1	c.-11G>A		5_prime_UTR_variant	1/2		NP_001311121.1
PANK2	NM_153638.4	c.-11G>A		5_prime_UTR_variant	1/7		NP_705902.2
PANK2	NM_024960.6	c.-246+186G>A		intron_variant			NP_079236.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PANK2	ENST00000316562.9	c.-11G>A		5_prime_UTR_variant	1/7	1		ENSP00000313377	A2
PANK2-AS1	ENST00000702266.1	n.84C>T		non_coding_transcript_exon_variant	1/1
PANK2	ENST00000495692.5	c.-538+74G>A		intron_variant		3		ENSP00000476745
PANK2	ENST00000497424.5	c.-246+186G>A		intron_variant		2		ENSP00000417609

Frequencies

GnomAD3 genomes AF: 0.00256 AC: 389 AN: 152152 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.000555

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0648

Gnomad SAS AF: 0.00393

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00143

GnomAD3 exomes AF: 0.00526 AC: 741 AN: 140928 Hom.: 29 AF XY: 0.00506 AC XY: 379 AN XY: 74954

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000209

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0644

Gnomad SAS exome AF: 0.000810

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000959

Gnomad OTH exome AF: 0.00172

GnomAD4 exome AF: 0.00167 AC: 2314 AN: 1381760 Hom.: 73 Cov.: 30 AF XY: 0.00163 AC XY: 1105 AN XY: 679952

Gnomad4 AFR exome AF: 0.0000958

Gnomad4 AMR exome AF: 0.000172

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0537

Gnomad4 SAS exome AF: 0.00135

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000813

Gnomad4 OTH exome AF: 0.00346

GnomAD4 genome AF: 0.00252 AC: 384 AN: 152270 Hom.: 6 Cov.: 32 AF XY: 0.00286 AC XY: 213 AN XY: 74454

Gnomad4 AFR AF: 0.000553

Gnomad4 AMR AF: 0.000131

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0639

Gnomad4 SAS AF: 0.00393

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000118

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.000214 Hom.: 0

Bravo AF: 0.00259

Asia WGS AF: 0.0260 AC: 89 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Feb 14, 2018	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 05, 2018	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

May 30, 2016

- -

Pigmentary pallidal degeneration Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	4.9
DANN	Benign	0.81

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs71647826; hg19: chr20-3869737;