20-3889079-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The ENST00000316562.9(PANK2):c.-22G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00328 in 1,520,538 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0026 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0033 (24 hom.)
• Consequence: PANK2 ENST00000316562.9 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0650

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 20-3889079-G-C is Benign according to our data. Variant chr20-3889079-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 1194321.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00265 (403/152158) while in subpopulation EAS AF= 0.033 (170/5146). AF 95% confidence interval is 0.029. There are 1 homozygotes in gnomad4. There are 187 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome at 5 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PANK2-AS1	XR_001754478.3	n.95C>G		non_coding_transcript_exon_variant	1/2
PANK2	NM_001324192.1	c.-22G>C		5_prime_UTR_variant	1/2
PANK2	NM_153638.4	c.-22G>C		5_prime_UTR_variant	1/7
PANK2	NM_024960.6	c.-246+175G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PANK2	ENST00000316562.9	c.-22G>C		5_prime_UTR_variant	1/7	1		A2
PANK2-AS1	ENST00000702266.1	n.95C>G		non_coding_transcript_exon_variant	1/1
PANK2	ENST00000495692.5	c.-538+63G>C		intron_variant		3
PANK2	ENST00000497424.5	c.-246+175G>C		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.00264 AC: 402 AN: 152040 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000942

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000720

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0328

Gnomad SAS AF: 0.00103

Gnomad FIN AF: 0.000283

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00244

Gnomad OTH AF: 0.00431

GnomAD3 exomes AF: 0.00395 AC: 517 AN: 131030 Hom.: 5 AF XY: 0.00379 AC XY: 263 AN XY: 69312

Gnomad AFR exome AF: 0.000550

Gnomad AMR exome AF: 0.000812

Gnomad ASJ exome AF: 0.000316

Gnomad EAS exome AF: 0.0325

Gnomad SAS exome AF: 0.000319

Gnomad FIN exome AF: 0.000316

Gnomad NFE exome AF: 0.00249

Gnomad OTH exome AF: 0.00234

GnomAD4 exome AF: 0.00335 AC: 4580 AN: 1368380 Hom.: 24 Cov.: 29 AF XY: 0.00326 AC XY: 2193 AN XY: 672588

Gnomad4 AFR exome AF: 0.000449

Gnomad4 AMR exome AF: 0.000958

Gnomad4 ASJ exome AF: 0.000430

Gnomad4 EAS exome AF: 0.0252

Gnomad4 SAS exome AF: 0.000504

Gnomad4 FIN exome AF: 0.000485

Gnomad4 NFE exome AF: 0.00312

Gnomad4 OTH exome AF: 0.00439

GnomAD4 genome AF: 0.00265 AC: 403 AN: 152158 Hom.: 1 Cov.: 32 AF XY: 0.00251 AC XY: 187 AN XY: 74406

Gnomad4 AFR AF: 0.000939

Gnomad4 AMR AF: 0.000719

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0330

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.000283

Gnomad4 NFE AF: 0.00244

Gnomad4 OTH AF: 0.00426

Alfa AF: 0.000719 Hom.: 1

Bravo AF: 0.00265

Asia WGS AF: 0.0130 AC: 44 AN: 3478

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

Sep 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
Cadd	Benign	4.8
Dann	Benign	0.37
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: rs199787176; hg19: chr20-3869726;