rs152296

Variant names:

• chr3-64129771-G-A
• rs152296
• NM_198859.4:c.1660+17059C>T

Variant summary

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

The NM_198859.4(PRICKLE2):​c.1660+17059C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.479 in 151,802 control chromosomes in the GnomAD database, including 18,028 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 0.48 (18028 hom., cov: 31)
• Consequence: PRICKLE2 NM_198859.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.227
• Publications: 3 publications found

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]

PRICKLE2 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen
• neurodevelopmental disorder

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.809 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRICKLE2	NM_198859.4	c.1660+17059C>T		intron_variant	Intron 7 of 7	ENST00000638394.2	NP_942559.1
PRICKLE2	NM_001370528.1	c.1660+17059C>T		intron_variant	Intron 7 of 7		NP_001357457.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRICKLE2	ENST00000638394.2	c.1660+17059C>T		intron_variant	Intron 7 of 7	1	NM_198859.4	ENSP00000492363.1
PRICKLE2	ENST00000295902.11	c.1828+17059C>T		intron_variant	Intron 8 of 8	5		ENSP00000295902.7
PRICKLE2	ENST00000564377.6	c.1660+17059C>T		intron_variant	Intron 7 of 7	5		ENSP00000455004.2
PRICKLE2	ENST00000640303.1	n.2299+17059C>T		intron_variant	Intron 5 of 5	5

Frequencies

GnomAD3 genomes AF: 0.479 AC: 72687 AN: 151684 Hom.: 18010 Cov.: 31

Gnomad AFR AF: 0.472

Gnomad AMI AF: 0.646

Gnomad AMR AF: 0.516

Gnomad ASJ AF: 0.370

Gnomad EAS AF: 0.831

Gnomad SAS AF: 0.548

Gnomad FIN AF: 0.581

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.433

Gnomad OTH AF: 0.461

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

GnomAD4 genome AF: 0.479 AC: 72740 AN: 151802 Hom.: 18028 Cov.: 31 AF XY: 0.490 AC XY: 36316 AN XY: 74156

African (AFR) AF: 0.471 AC: 19498 AN: 41376

American (AMR) AF: 0.516 AC: 7875 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.370 AC: 1283 AN: 3464

East Asian (EAS) AF: 0.830 AC: 4276 AN: 5152

South Asian (SAS) AF: 0.545 AC: 2618 AN: 4800

European-Finnish (FIN) AF: 0.581 AC: 6106 AN: 10508

Middle Eastern (MID) AF: 0.367 AC: 108 AN: 294

European-Non Finnish (NFE) AF: 0.433 AC: 29404 AN: 67942

Other (OTH) AF: 0.467 AC: 985 AN: 2110

Alfa AF: 0.443 Hom.: 7846

Bravo AF: 0.471

Asia WGS AF: 0.695 AC: 2414 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	11
DANN	Benign	0.83
PhyloP100		0.23
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: rs152296; hg19: chr3-64115447;