rs741013

chr3-64306961-A-T

Variant summary

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

The ENST00000295902.11(PRICKLE2):c.129-107994T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0601 in 152,294 control chromosomes in the GnomAD database, including 358 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 0.060 (358 hom., cov: 32)
• Consequence: PRICKLE2 ENST00000295902.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.69

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=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0864 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRICKLE2	ENST00000295902.11	c.129-107994T>A		intron_variant		5		P1
PRICKLE2	ENST00000498162.2	c.110-107994T>A		intron_variant		5
PRICKLE2	ENST00000485770.2	n.341-107994T>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0601 AC: 9149 AN: 152176 Hom.: 358 Cov.: 32

Gnomad AFR AF: 0.0218

Gnomad AMI AF: 0.0373

Gnomad AMR AF: 0.0647

Gnomad ASJ AF: 0.0982

Gnomad EAS AF: 0.00308

Gnomad SAS AF: 0.0934

Gnomad FIN AF: 0.0662

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0817

Gnomad OTH AF: 0.0669

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

GnomAD4 genome AF: 0.0601 AC: 9152 AN: 152294 Hom.: 358 Cov.: 32 AF XY: 0.0603 AC XY: 4493 AN XY: 74460

Gnomad4 AFR AF: 0.0218

Gnomad4 AMR AF: 0.0646

Gnomad4 ASJ AF: 0.0982

Gnomad4 EAS AF: 0.00309

Gnomad4 SAS AF: 0.0935

Gnomad4 FIN AF: 0.0662

Gnomad4 NFE AF: 0.0816

Gnomad4 OTH AF: 0.0685

Alfa AF: 0.0701 Hom.: 46

Bravo AF: 0.0571

Asia WGS AF: 0.0600 AC: 209 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	6.1
Dann	Benign	0.65

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs741013; hg19: chr3-64292637;