rs1443529

Positions:

• chr3-64413843-C-A

Variant summary

Our verdict is Benign. Variant got -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

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=-0.83).
• 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/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRICKLE2	ENST00000295902.11	c.128+30640G>T		intron_variant		5		ENSP00000295902	P1
PRICKLE2	ENST00000498162.2	c.109+30640G>T		intron_variant		5		ENSP00000419951
PRICKLE2	ENST00000485770.2	n.340+30640G>T		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.0563

Gnomad4 AMR AF: 0.229

Gnomad4 ASJ AF: 0.186

Gnomad4 EAS AF: 0.602

Gnomad4 SAS AF: 0.162

Gnomad4 FIN AF: 0.172

Gnomad4 NFE AF: 0.188

Gnomad4 OTH AF: 0.197

Alfa AF: 0.173 Hom.: 312

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1443529; hg19: chr3-64399519;