20-3889048-G-A

Variant names:

• chr20-3889048-G-A
• rs564516235
• ENST00000316562:c.-53G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_153638.4(PANK2):​c.-53G>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 0.00151 in 1,435,908 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0016 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0015 (4 hom.)
• Consequence: PANK2 NM_153638.4 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.523

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

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 20-3889048-G-A is Benign according to our data. Variant chr20-3889048-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1197052.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00165 (250/151690) while in subpopulation NFE AF = 0.0014 (95/67826). AF 95% confidence interval is 0.00117. There are 0 homozygotes in GnomAd4. There are 157 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position FAILED quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 4 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PANK2	NM_153638.4	c.-53G>A		5_prime_UTR_variant	Exon 1 of 7		NP_705902.2
PANK2	NM_001324192.1	c.-53G>A		5_prime_UTR_variant	Exon 1 of 2		NP_001311121.1
PANK2	NM_024960.6	c.-246+144G>A		intron_variant	Intron 1 of 6		NP_079236.3
PANK2-AS1	XR_001754478.3	n.126C>T		non_coding_transcript_exon_variant	Exon 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PANK2	ENST00000316562	c.-53G>A		5_prime_UTR_variant	Exon 1 of 7	1		ENSP00000313377.4
PANK2	ENST00000497424.5	c.-246+144G>A		intron_variant	Intron 1 of 6	2		ENSP00000417609.1
PANK2	ENST00000495692.5	c.-538+32G>A		intron_variant	Intron 1 of 5	3		ENSP00000476745.1

Frequencies

GnomAD3 genomes AF: 0.00165 AC: 250 AN: 151572 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000267

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000590

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0126

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00140

Gnomad OTH AF: 0.000482

GnomAD4 exome AF: 0.00150 AC: 1925 AN: 1284218 Hom.: 4 Cov.: 24 AF XY: 0.00145 AC XY: 915 AN XY: 629092

Gnomad4 AFR exome AF: 0.000375 AC: 11 AN: 29348

Gnomad4 AMR exome AF: 0.000938 AC: 27 AN: 28772

Gnomad4 ASJ exome AF: 0.0000970 AC: 2 AN: 20612

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 35032

Gnomad4 SAS exome AF: 0.0000145 AC: 1 AN: 69006

Gnomad4 FIN exome AF: 0.00696 AC: 267 AN: 38360

Gnomad4 NFE exome AF: 0.00153 AC: 1540 AN: 1005944

Gnomad4 Remaining exome AF: 0.00142 AC: 76 AN: 53456

GnomAD4 genome AF: 0.00165 AC: 250 AN: 151690 Hom.: 0 Cov.: 32 AF XY: 0.00212 AC XY: 157 AN XY: 74174

Gnomad4 AFR AF: 0.000266 AC: 0.000266022 AN: 0.000266022

Gnomad4 AMR AF: 0.000589 AC: 0.000589314 AN: 0.000589314

Gnomad4 ASJ AF: 0.000288 AC: 0.000288351 AN: 0.000288351

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.00 AC: 0 AN: 0

Gnomad4 FIN AF: 0.0126 AC: 0.0125852 AN: 0.0125852

Gnomad4 NFE AF: 0.00140 AC: 0.00140064 AN: 0.00140064

Gnomad4 OTH AF: 0.000477 AC: 0.000476644 AN: 0.000476644

Alfa AF: 0.00108 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jul 26, 2019

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	2.5
DANN	Benign	0.96
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3
Mutation Taster		=100/0	polymorphism

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs564516235; hg19: chr20-3869695;