rs888405

Positions:

• chr3-64216026-A-G

Variant summary

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

The NM_198859.4(PRICKLE2):​c.-41+8884T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.658 in 152,180 control chromosomes in the GnomAD database, including 35,867 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 0.66 (35867 hom., cov: 33)
• Consequence: PRICKLE2 NM_198859.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0350

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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.794 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRICKLE2	NM_198859.4	c.-41+8884T>C		intron_variant		ENST00000638394.2
PRICKLE2	NM_001370528.1	c.-40-17059T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRICKLE2	ENST00000638394.2	c.-41+8884T>C		intron_variant		1	NM_198859.4

Frequencies

GnomAD3 genomes AF: 0.658 AC: 100044 AN: 152062 Hom.: 35856 Cov.: 33

Gnomad AFR AF: 0.350

Gnomad AMI AF: 0.740

Gnomad AMR AF: 0.713

Gnomad ASJ AF: 0.809

Gnomad EAS AF: 0.509

Gnomad SAS AF: 0.758

Gnomad FIN AF: 0.834

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.800

Gnomad OTH AF: 0.693

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

GnomAD4 genome AF: 0.658 AC: 100075 AN: 152180 Hom.: 35867 Cov.: 33 AF XY: 0.662 AC XY: 49232 AN XY: 74390

Gnomad4 AFR AF: 0.350

Gnomad4 AMR AF: 0.713

Gnomad4 ASJ AF: 0.809

Gnomad4 EAS AF: 0.508

Gnomad4 SAS AF: 0.758

Gnomad4 FIN AF: 0.834

Gnomad4 NFE AF: 0.800

Gnomad4 OTH AF: 0.699

Alfa AF: 0.771 Hom.: 88921

Bravo AF: 0.631

Asia WGS AF: 0.648 AC: 2256 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.1
DANN	Benign	0.57

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: rs888405; hg19: chr3-64201702;