rs4688187

Positions:

• chr3-64386931-G-A

Variant summary

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

The ENST00000295902.11(PRICKLE2):​c.128+57552C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.536 in 152,060 control chromosomes in the GnomAD database, including 25,139 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 0.54 (25139 hom., cov: 33)
• Consequence: PRICKLE2 ENST00000295902.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.172

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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.836 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+57552C>T		intron_variant		5		ENSP00000295902	P1
PRICKLE2	ENST00000498162.2	c.109+57552C>T		intron_variant		5		ENSP00000419951
PRICKLE2	ENST00000485770.2	n.340+57552C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.535 AC: 81340 AN: 151942 Hom.: 25087 Cov.: 33

Gnomad AFR AF: 0.823

Gnomad AMI AF: 0.230

Gnomad AMR AF: 0.524

Gnomad ASJ AF: 0.377

Gnomad EAS AF: 0.858

Gnomad SAS AF: 0.565

Gnomad FIN AF: 0.492

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.356

Gnomad OTH AF: 0.504

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

GnomAD4 genome AF: 0.536 AC: 81453 AN: 152060 Hom.: 25139 Cov.: 33 AF XY: 0.546 AC XY: 40586 AN XY: 74334

Gnomad4 AFR AF: 0.823

Gnomad4 AMR AF: 0.524

Gnomad4 ASJ AF: 0.377

Gnomad4 EAS AF: 0.857

Gnomad4 SAS AF: 0.566

Gnomad4 FIN AF: 0.492

Gnomad4 NFE AF: 0.356

Gnomad4 OTH AF: 0.499

Alfa AF: 0.454 Hom.: 5733

Bravo AF: 0.553

Asia WGS AF: 0.690 AC: 2395 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.77
DANN	Benign	0.70

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4688187; hg19: chr3-64372607; COSMIC: COSV73860787;