rs1860819

Positions:

• chr3-64363278-A-G
• chr3-64363278-A-T

Variant summary

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

The ENST00000295902.11(PRICKLE2):​c.128+81205T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.163 in 152,086 control chromosomes in the GnomAD database, including 2,902 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 0.16 (2902 hom., cov: 32)
• Consequence: PRICKLE2 ENST00000295902.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0300

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.67 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.64363278A>G		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRICKLE2	ENST00000295902.11	c.128+81205T>C		intron_variant		5		ENSP00000295902.7
PRICKLE2	ENST00000498162.2	c.107+81205T>C		intron_variant		5		ENSP00000419951.2
PRICKLE2	ENST00000485770.2	n.340+81205T>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.163 AC: 24813 AN: 151968 Hom.: 2898 Cov.: 32

Gnomad AFR AF: 0.123

Gnomad AMI AF: 0.174

Gnomad AMR AF: 0.191

Gnomad ASJ AF: 0.150

Gnomad EAS AF: 0.689

Gnomad SAS AF: 0.227

Gnomad FIN AF: 0.198

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.133

Gnomad OTH AF: 0.152

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

GnomAD4 genome AF: 0.163 AC: 24839 AN: 152086 Hom.: 2902 Cov.: 32 AF XY: 0.170 AC XY: 12608 AN XY: 74318

Gnomad4 AFR AF: 0.124

Gnomad4 AMR AF: 0.191

Gnomad4 ASJ AF: 0.150

Gnomad4 EAS AF: 0.689

Gnomad4 SAS AF: 0.229

Gnomad4 FIN AF: 0.198

Gnomad4 NFE AF: 0.132

Gnomad4 OTH AF: 0.151

Alfa AF: 0.143 Hom.: 2245

Bravo AF: 0.165

Asia WGS AF: 0.411 AC: 1425 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	9.2
DANN	Benign	0.85

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1860819; hg19: chr3-64348954;