Variant 20-3889079-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

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

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0650

Variant links:

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 links:

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

PANK2-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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 GnomAdExome4 at 24 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	Protein
PANK2-AS1	XR_001754478.3 linkuse as main transcript	n.95C>G	non_coding_transcript_exon_variant	1/2
PANK2	NM_001324192.1 linkuse as main transcript	c.-22G>C	5_prime_UTR_variant	1/2	NP_001311121.1
PANK2	NM_153638.4 linkuse as main transcript	c.-22G>C	5_prime_UTR_variant	1/7	NP_705902.2
PANK2	NM_024960.6 linkuse as main transcript	c.-246+175G>C	intron_variant		NP_079236.3

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	Protein	Appris	UniProt
PANK2	ENST00000316562.9 linkuse as main transcript	c.-22G>C	5_prime_UTR_variant	1/7	1	ENSP00000313377	A2	Q9BZ23-1
PANK2-AS1	ENST00000702266.1 linkuse as main transcript	n.95C>G	non_coding_transcript_exon_variant	1/1
PANK2	ENST00000495692.5 linkuse as main transcript	c.-538+63G>C	intron_variant		3	ENSP00000476745
PANK2	ENST00000497424.5 linkuse as main transcript	c.-246+175G>C	intron_variant		2	ENSP00000417609		Q9BZ23-2

Frequencies

GnomAD3 genomes

AF:

0.00264

AC:

402

AN:

152040

Hom.:

Cov.:

show subpopulations

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.:

AF XY:

0.00379

AC XY:

263

AN XY:

69312

show subpopulations

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.:

Cov.:

AF XY:

0.00326

AC XY:

2193

AN XY:

672588

show subpopulations

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.:

Cov.:

AF XY:

0.00251

AC XY:

187

AN XY:

74406

show subpopulations

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.:

Bravo

AF:

0.00265

Asia WGS

AF:

0.0130

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over