rs2849589

Variant names:

• chr6-162164722-T-C
• rs2849589
• NM_004562.3:c.534+36409A>G

Variant summary

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

The NM_004562.3(PRKN):​c.534+36409A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0721 in 148,936 control chromosomes in the GnomAD database, including 1,413 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 0.072 (1413 hom., cov: 31)
• Consequence: PRKN NM_004562.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.14
• Publications: 0 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.395 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKN	NM_004562.3	c.534+36409A>G		intron_variant	Intron 4 of 11	ENST00000366898.6	NP_004553.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKN	ENST00000366898.6	c.534+36409A>G		intron_variant	Intron 4 of 11	1	NM_004562.3	ENSP00000355865.1

Frequencies

GnomAD3 genomes AF: 0.0722 AC: 10739 AN: 148840 Hom.: 1407 Cov.: 31

Gnomad AFR AF: 0.0951

Gnomad AMI AF: 0.0115

Gnomad AMR AF: 0.116

Gnomad ASJ AF: 0.0268

Gnomad EAS AF: 0.409

Gnomad SAS AF: 0.0961

Gnomad FIN AF: 0.0480

Gnomad MID AF: 0.0288

Gnomad NFE AF: 0.0283

Gnomad OTH AF: 0.0812

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

GnomAD4 genome AF: 0.0721 AC: 10745 AN: 148936 Hom.: 1413 Cov.: 31 AF XY: 0.0768 AC XY: 5591 AN XY: 72822

African (AFR) AF: 0.0950 AC: 3768 AN: 39658

American (AMR) AF: 0.116 AC: 1725 AN: 14932

Ashkenazi Jewish (ASJ) AF: 0.0268 AC: 92 AN: 3432

East Asian (EAS) AF: 0.409 AC: 2107 AN: 5148

South Asian (SAS) AF: 0.0962 AC: 456 AN: 4742

European-Finnish (FIN) AF: 0.0480 AC: 502 AN: 10464

Middle Eastern (MID) AF: 0.0241 AC: 7 AN: 290

European-Non Finnish (NFE) AF: 0.0283 AC: 1907 AN: 67346

Other (OTH) AF: 0.0832 AC: 171 AN: 2056

Alfa AF: 0.0481 Hom.: 97

Asia WGS AF: 0.234 AC: 806 AN: 3456

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.0040
DANN	Benign	0.57
PhyloP100		-2.1
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: rs2849589; hg19: chr6-162585754;