rs853256

Variant names:

• chr3-64329788-A-G
• rs853256
• ENST00000295902.11:c.128+114695T>C

Variant summary

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

The ENST00000295902.11(PRICKLE2):​c.128+114695T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.293 in 151,954 control chromosomes in the GnomAD database, including 8,198 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 0.29 (8198 hom., cov: 32)
• Consequence: PRICKLE2 ENST00000295902.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.54
• Publications: 4 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.513 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+114695T>C		intron_variant	Intron 2 of 8	5		ENSP00000295902.7
PRICKLE2	ENST00000498162.2	c.107+114695T>C		intron_variant	Intron 2 of 4	5		ENSP00000419951.2
PRICKLE2	ENST00000485770.2	n.340+114695T>C		intron_variant	Intron 2 of 3	5

Frequencies

GnomAD3 genomes AF: 0.293 AC: 44421 AN: 151836 Hom.: 8159 Cov.: 32

Gnomad AFR AF: 0.519

Gnomad AMI AF: 0.0560

Gnomad AMR AF: 0.335

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.120

Gnomad SAS AF: 0.263

Gnomad FIN AF: 0.186

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.188

Gnomad OTH AF: 0.271

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

GnomAD4 genome AF: 0.293 AC: 44519 AN: 151954 Hom.: 8198 Cov.: 32 AF XY: 0.295 AC XY: 21895 AN XY: 74272

African (AFR) AF: 0.519 AC: 21505 AN: 41420

American (AMR) AF: 0.336 AC: 5121 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.164 AC: 570 AN: 3468

East Asian (EAS) AF: 0.121 AC: 624 AN: 5176

South Asian (SAS) AF: 0.262 AC: 1262 AN: 4812

European-Finnish (FIN) AF: 0.186 AC: 1955 AN: 10530

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.188 AC: 12801 AN: 67990

Other (OTH) AF: 0.271 AC: 572 AN: 2110

Alfa AF: 0.214 Hom.: 2030

Bravo AF: 0.314

Asia WGS AF: 0.253 AC: 876 AN: 3458

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.26
DANN	Benign	0.50
PhyloP100		-1.5
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: rs853256; hg19: chr3-64315464;