rs2155510

Positions:

• chr6-162573607-T-C
• chr6-162573607-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004562.3(PRKN):​c.8-130134A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.531 in 152,032 control chromosomes in the GnomAD database, including 21,722 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 0.53 (21722 hom., cov: 32)
• Consequence: PRKN NM_004562.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.74

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.691 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRKN	NM_004562.3	c.8-130134A>G		intron_variant		ENST00000366898.6	NP_004553.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRKN	ENST00000366898.6	c.8-130134A>G		intron_variant		1	NM_004562.3	ENSP00000355865.1

Frequencies

GnomAD3 genomes AF: 0.531 AC: 80625 AN: 151914 Hom.: 21692 Cov.: 32

Gnomad AFR AF: 0.574

Gnomad AMI AF: 0.688

Gnomad AMR AF: 0.536

Gnomad ASJ AF: 0.456

Gnomad EAS AF: 0.710

Gnomad SAS AF: 0.619

Gnomad FIN AF: 0.509

Gnomad MID AF: 0.583

Gnomad NFE AF: 0.488

Gnomad OTH AF: 0.529

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

GnomAD4 genome AF: 0.531 AC: 80696 AN: 152032 Hom.: 21722 Cov.: 32 AF XY: 0.536 AC XY: 39837 AN XY: 74320

Gnomad4 AFR AF: 0.575

Gnomad4 AMR AF: 0.536

Gnomad4 ASJ AF: 0.456

Gnomad4 EAS AF: 0.710

Gnomad4 SAS AF: 0.617

Gnomad4 FIN AF: 0.509

Gnomad4 NFE AF: 0.488

Gnomad4 OTH AF: 0.529

Alfa AF: 0.511 Hom.: 7084

Bravo AF: 0.535

Asia WGS AF: 0.634 AC: 2204 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.36
DANN	Benign	0.52

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

Publications

LitVar

Other links and lift over

dbSNP: rs2155510; hg19: chr6-162994639; COSMIC: COSV58211671; COSMIC: COSV58211671;