rs2803073

Variant names:

• chr6-162541796-G-A
• rs2803073
• NM_004562.3:c.8-98323C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004562.3(PRKN):​c.8-98323C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.735 in 151,912 control chromosomes in the GnomAD database, including 41,983 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.74 (41983 hom., cov: 32)
• Consequence: PRKN NM_004562.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0630
• Publications: 5 publications found

Genes affected

PRKN (HGNC:8607): (parkin RBR E3 ubiquitin protein ligase) The precise function of this gene is unknown; however, the encoded protein is a component of a multiprotein E3 ubiquitin ligase complex that mediates the targeting of substrate proteins for proteasomal degradation. Mutations in this gene are known to cause Parkinson disease and autosomal recessive juvenile Parkinson disease. Alternative splicing of this gene produces multiple transcript variants encoding distinct isoforms. Additional splice variants of this gene have been described but currently lack transcript support. [provided by RefSeq, Jul 2008]

PRKN Gene-Disease associations (from GenCC):

• autosomal recessive juvenile Parkinson disease 2

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Laboratory for Molecular Medicine, Genomics England PanelApp
• Parkinson disease

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• young-onset Parkinson disease

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.817 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKN	NM_004562.3	c.8-98323C>T		intron_variant	Intron 1 of 11	ENST00000366898.6	NP_004553.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKN	ENST00000366898.6	c.8-98323C>T		intron_variant	Intron 1 of 11	1	NM_004562.3	ENSP00000355865.1

Frequencies

GnomAD3 genomes AF: 0.735 AC: 111632 AN: 151794 Hom.: 41935 Cov.: 32

Gnomad AFR AF: 0.824

Gnomad AMI AF: 0.681

Gnomad AMR AF: 0.681

Gnomad ASJ AF: 0.810

Gnomad EAS AF: 0.259

Gnomad SAS AF: 0.687

Gnomad FIN AF: 0.672

Gnomad MID AF: 0.775

Gnomad NFE AF: 0.740

Gnomad OTH AF: 0.731

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.735 AC: 111727 AN: 151912 Hom.: 41983 Cov.: 32 AF XY: 0.727 AC XY: 53952 AN XY: 74218

African (AFR) AF: 0.824 AC: 34145 AN: 41420

American (AMR) AF: 0.681 AC: 10393 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.810 AC: 2808 AN: 3468

East Asian (EAS) AF: 0.258 AC: 1328 AN: 5156

South Asian (SAS) AF: 0.688 AC: 3314 AN: 4818

European-Finnish (FIN) AF: 0.672 AC: 7081 AN: 10534

Middle Eastern (MID) AF: 0.786 AC: 231 AN: 294

European-Non Finnish (NFE) AF: 0.740 AC: 50273 AN: 67942

Other (OTH) AF: 0.729 AC: 1536 AN: 2108

Alfa AF: 0.744 Hom.: 48658

Bravo AF: 0.735

Asia WGS AF: 0.542 AC: 1889 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.3
DANN	Benign	0.52
PhyloP100		0.063
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs2803073; hg19: chr6-162962828; COSMIC: COSV58269005;