rs853260

Positions:

• chr3-64328876-G-A
• chr3-64328876-G-C

Variant summary

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

The ENST00000295902.11(PRICKLE2):​c.128+115607C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.289 in 151,996 control chromosomes in the GnomAD database, including 8,087 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 (8087 hom., cov: 32)
• Consequence: PRICKLE2 ENST00000295902.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.392

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 (AFR) allele frequency at 95% confidence interval = 0.511 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.128+115607C>T		intron_variant		5		P1
PRICKLE2	ENST00000498162.2	c.109+115607C>T		intron_variant		5
PRICKLE2	ENST00000485770.2	n.340+115607C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.289 AC: 43861 AN: 151878 Hom.: 8050 Cov.: 32

Gnomad AFR AF: 0.516

Gnomad AMI AF: 0.0559

Gnomad AMR AF: 0.334

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.117

Gnomad SAS AF: 0.262

Gnomad FIN AF: 0.178

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.183

Gnomad OTH AF: 0.269

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

GnomAD4 genome AF: 0.289 AC: 43953 AN: 151996 Hom.: 8087 Cov.: 32 AF XY: 0.291 AC XY: 21613 AN XY: 74296

Gnomad4 AFR AF: 0.517

Gnomad4 AMR AF: 0.335

Gnomad4 ASJ AF: 0.164

Gnomad4 EAS AF: 0.117

Gnomad4 SAS AF: 0.261

Gnomad4 FIN AF: 0.178

Gnomad4 NFE AF: 0.183

Gnomad4 OTH AF: 0.269

Alfa AF: 0.187 Hom.: 4640

Bravo AF: 0.311

Asia WGS AF: 0.252 AC: 879 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.5
DANN	Benign	0.64

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs853260; hg19: chr3-64314552;