rs7615058

Positions:

• chr3-64360324-C-A
• chr3-64360324-C-G

Variant summary

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

The ENST00000295902.11(PRICKLE2):​c.128+84159G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.369 in 151,914 control chromosomes in the GnomAD database, including 14,181 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 0.37 (14181 hom., cov: 31)
• Consequence: PRICKLE2 ENST00000295902.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.901

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.715 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+84159G>T		intron_variant		5		P1
PRICKLE2	ENST00000498162.2	c.109+84159G>T		intron_variant		5
PRICKLE2	ENST00000485770.2	n.340+84159G>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.368 AC: 55916 AN: 151796 Hom.: 14136 Cov.: 31

Gnomad AFR AF: 0.722

Gnomad AMI AF: 0.185

Gnomad AMR AF: 0.377

Gnomad ASJ AF: 0.207

Gnomad EAS AF: 0.254

Gnomad SAS AF: 0.277

Gnomad FIN AF: 0.196

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.206

Gnomad OTH AF: 0.331

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

GnomAD4 genome AF: 0.369 AC: 56017 AN: 151914 Hom.: 14181 Cov.: 31 AF XY: 0.369 AC XY: 27381 AN XY: 74248

Gnomad4 AFR AF: 0.722

Gnomad4 AMR AF: 0.377

Gnomad4 ASJ AF: 0.207

Gnomad4 EAS AF: 0.254

Gnomad4 SAS AF: 0.276

Gnomad4 FIN AF: 0.196

Gnomad4 NFE AF: 0.206

Gnomad4 OTH AF: 0.331

Alfa AF: 0.249 Hom.: 4314

Bravo AF: 0.400

Asia WGS AF: 0.303 AC: 1053 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.10
DANN	Benign	0.69

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7615058; hg19: chr3-64346000;