rs149105

chr3-64175286-T-Achr3-64175286-T-G

Variant summary

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

The NM_198859.4(PRICKLE2):c.145-12157A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.425 in 152,898 control chromosomes in the GnomAD database, including 14,373 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 0.43 (14308 hom., cov: 32)
  • Exomes 𝑓: 0.38 (65 hom.)
• Consequence: PRICKLE2 NM_198859.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0990

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.543 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRICKLE2	NM_198859.4	c.145-12157A>T		intron_variant		ENST00000638394.2
PRICKLE2	NM_001370528.1	c.145-12157A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRICKLE2	ENST00000638394.2	c.145-12157A>T		intron_variant		1	NM_198859.4
PRICKLE2	ENST00000295902.11	c.313-12157A>T		intron_variant		5		P1
PRICKLE2	ENST00000498162.2	c.294-12157A>T		intron_variant		5
PRICKLE2	ENST00000564377.6	c.145-12157A>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.425 AC: 64481 AN: 151798 Hom.: 14276 Cov.: 32

Gnomad AFR AF: 0.549

Gnomad AMI AF: 0.366

Gnomad AMR AF: 0.328

Gnomad ASJ AF: 0.398

Gnomad EAS AF: 0.460

Gnomad SAS AF: 0.396

Gnomad FIN AF: 0.389

Gnomad MID AF: 0.379

Gnomad NFE AF: 0.380

Gnomad OTH AF: 0.388

GnomAD4 exome AF: 0.384 AC: 376 AN: 980 Hom.: 65 AF XY: 0.388 AC XY: 188 AN XY: 484

Gnomad4 AFR exome AF: 0.375

Gnomad4 AMR exome AF: 0.300

Gnomad4 ASJ exome AF: 0.500

Gnomad4 SAS exome AF: 0.600

Gnomad4 FIN exome AF: 0.385

Gnomad4 NFE exome AF: 0.358

Gnomad4 OTH exome AF: 0.458

GnomAD4 genome AF: 0.425 AC: 64573 AN: 151918 Hom.: 14308 Cov.: 32 AF XY: 0.423 AC XY: 31423 AN XY: 74256

Gnomad4 AFR AF: 0.549

Gnomad4 AMR AF: 0.328

Gnomad4 ASJ AF: 0.398

Gnomad4 EAS AF: 0.460

Gnomad4 SAS AF: 0.397

Gnomad4 FIN AF: 0.389

Gnomad4 NFE AF: 0.380

Gnomad4 OTH AF: 0.387

Alfa AF: 0.407 Hom.: 1568

Bravo AF: 0.426

Asia WGS AF: 0.411 AC: 1432 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	0.74
Dann	Benign	0.86

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs149105; hg19: chr3-64160962;