rs153717

Positions:

• chr3-64186317-G-A
• chr3-64186317-G-C

Variant summary

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

The NM_198859.4(PRICKLE2):​c.144+12467C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.419 in 151,986 control chromosomes in the GnomAD database, including 13,950 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 0.42 (13950 hom., cov: 33)
• Consequence: PRICKLE2 NM_198859.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.287

Genes affected

PRICKLE2 (HGNC:20340): (prickle planar cell polarity protein 2) This gene encodes a homolog of Drosophila prickle. The exact function of this gene is not known, however, studies in mice suggest that it may be involved in seizure prevention. Mutations in this gene are associated with progressive myoclonic epilepsy type 5. [provided by RefSeq, Dec 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.542 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRICKLE2	NM_198859.4	c.144+12467C>T		intron_variant		ENST00000638394.2	NP_942559.1
PRICKLE2	NM_001370528.1	c.144+12467C>T		intron_variant			NP_001357457.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRICKLE2	ENST00000638394.2	c.144+12467C>T		intron_variant		1	NM_198859.4	ENSP00000492363

Frequencies

GnomAD3 genomes AF: 0.418 AC: 63531 AN: 151868 Hom.: 13918 Cov.: 33

Gnomad AFR AF: 0.548

Gnomad AMI AF: 0.388

Gnomad AMR AF: 0.337

Gnomad ASJ AF: 0.397

Gnomad EAS AF: 0.482

Gnomad SAS AF: 0.378

Gnomad FIN AF: 0.336

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.371

Gnomad OTH AF: 0.388

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

GnomAD4 genome AF: 0.419 AC: 63618 AN: 151986 Hom.: 13950 Cov.: 33 AF XY: 0.416 AC XY: 30872 AN XY: 74288

Gnomad4 AFR AF: 0.548

Gnomad4 AMR AF: 0.337

Gnomad4 ASJ AF: 0.397

Gnomad4 EAS AF: 0.483

Gnomad4 SAS AF: 0.380

Gnomad4 FIN AF: 0.336

Gnomad4 NFE AF: 0.371

Gnomad4 OTH AF: 0.387

Alfa AF: 0.379 Hom.: 23256

Bravo AF: 0.426

Asia WGS AF: 0.412 AC: 1434 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	1.6
DANN	Benign	0.21

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: rs153717; hg19: chr3-64171993;