20-3889048-G-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The ENST00000316562.9(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 ENST00000316562.9 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

Verdict is Likely_benign. Variant got -6 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PANK2-AS1	XR_001754478.3	n.126C>T		non_coding_transcript_exon_variant	1/2
PANK2	NM_001324192.1	c.-53G>A		5_prime_UTR_variant	1/2
PANK2	NM_153638.4	c.-53G>A		5_prime_UTR_variant	1/7
PANK2	NM_024960.6	c.-246+144G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PANK2	ENST00000316562.9	c.-53G>A		5_prime_UTR_variant	1/7	1		A2
PANK2-AS1	ENST00000702266.1	n.126C>T		non_coding_transcript_exon_variant	1/1
PANK2	ENST00000495692.5	c.-538+32G>A		intron_variant		3
PANK2	ENST00000497424.5	c.-246+144G>A		intron_variant		2

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

Gnomad4 AMR exome AF: 0.000938

Gnomad4 ASJ exome AF: 0.0000970

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000145

Gnomad4 FIN exome AF: 0.00696

Gnomad4 NFE exome AF: 0.00153

Gnomad4 OTH exome AF: 0.00142

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

Gnomad4 AMR AF: 0.000589

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0126

Gnomad4 NFE AF: 0.00140

Gnomad4 OTH AF: 0.000477

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

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 26, 2019

- -

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

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;