rs1443529

Variant names:

• chr3-64413843-C-A
• rs1443529
• ENST00000295902.11:c.128+30640G>T

Variant summary

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

The ENST00000295902.11(PRICKLE2):​c.128+30640G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.169 in 152,110 control chromosomes in the GnomAD database, including 3,075 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 0.17 (3075 hom., cov: 32)
• Consequence: PRICKLE2 ENST00000295902.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.814
• Publications: 1 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.585 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRICKLE2	ENST00000295902.11	c.128+30640G>T		intron_variant	Intron 2 of 8	5		ENSP00000295902.7
PRICKLE2	ENST00000498162.2	c.107+30640G>T		intron_variant	Intron 2 of 4	5		ENSP00000419951.2
PRICKLE2	ENST00000485770.2	n.340+30640G>T		intron_variant	Intron 2 of 3	5

Frequencies

GnomAD3 genomes AF: 0.169 AC: 25657 AN: 151992 Hom.: 3071 Cov.: 32

Gnomad AFR AF: 0.0563

Gnomad AMI AF: 0.213

Gnomad AMR AF: 0.229

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.602

Gnomad SAS AF: 0.161

Gnomad FIN AF: 0.172

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.188

Gnomad OTH AF: 0.199

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

GnomAD4 genome AF: 0.169 AC: 25662 AN: 152110 Hom.: 3075 Cov.: 32 AF XY: 0.171 AC XY: 12732 AN XY: 74360

African (AFR) AF: 0.0563 AC: 2339 AN: 41538

American (AMR) AF: 0.229 AC: 3503 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.186 AC: 647 AN: 3470

East Asian (EAS) AF: 0.602 AC: 3090 AN: 5130

South Asian (SAS) AF: 0.162 AC: 779 AN: 4820

European-Finnish (FIN) AF: 0.172 AC: 1820 AN: 10584

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.188 AC: 12798 AN: 67976

Other (OTH) AF: 0.197 AC: 416 AN: 2114

Alfa AF: 0.168 Hom.: 315

Bravo AF: 0.172

Asia WGS AF: 0.340 AC: 1179 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.62
DANN	Benign	0.49
PhyloP100		-0.81
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1443529; hg19: chr3-64399519;