3-64186317-G-A

Variant names:

• chr3-64186317-G-A
• rs153717
• NM_198859.4:c.144+12467C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_198859.4(PRICKLE2):​c.144+12467C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.419 in 151,986 control chromosomes in the GnomAD database, including 13,950 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 0.42 (13950 hom., cov: 33)
• Consequence: PRICKLE2 NM_198859.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.287
• Publications: 3 publications found

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]

PRICKLE2 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen
• neurodevelopmental disorder

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.542 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198859.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRICKLE2	NM_198859.4	MANE Select	c.144+12467C>T		intron	N/A	NP_942559.1
	PRICKLE2	NM_001370528.1		c.144+12467C>T		intron	N/A	NP_001357457.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRICKLE2	ENST00000638394.2	TSL:1 MANE Select	c.144+12467C>T		intron	N/A	ENSP00000492363.1
	PRICKLE2	ENST00000295902.11	TSL:5	c.312+12467C>T		intron	N/A	ENSP00000295902.7
	PRICKLE2	ENST00000564377.6	TSL:5	c.144+12467C>T		intron	N/A	ENSP00000455004.2

Frequencies

GnomAD3 genomes AF: 0.418 AC: 63531 AN: 151868 Hom.: 13918 Cov.: 33

Gnomad AFR AF: 0.548

Gnomad AMI AF: 0.388

Gnomad AMR AF: 0.337

Gnomad ASJ AF: 0.397

Gnomad EAS AF: 0.482

Gnomad SAS AF: 0.378

Gnomad FIN AF: 0.336

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.371

Gnomad OTH AF: 0.388

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

GnomAD4 genome AF: 0.419 AC: 63618 AN: 151986 Hom.: 13950 Cov.: 33 AF XY: 0.416 AC XY: 30872 AN XY: 74288

African (AFR) AF: 0.548 AC: 22719 AN: 41432

American (AMR) AF: 0.337 AC: 5154 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.397 AC: 1376 AN: 3468

East Asian (EAS) AF: 0.483 AC: 2491 AN: 5162

South Asian (SAS) AF: 0.380 AC: 1829 AN: 4816

European-Finnish (FIN) AF: 0.336 AC: 3542 AN: 10556

Middle Eastern (MID) AF: 0.381 AC: 112 AN: 294

European-Non Finnish (NFE) AF: 0.371 AC: 25224 AN: 67958

Other (OTH) AF: 0.387 AC: 818 AN: 2112

Alfa AF: 0.384 Hom.: 45656

Bravo AF: 0.426

Asia WGS AF: 0.412 AC: 1434 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.6
DANN	Benign	0.21
PhyloP100		0.29
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs153717; hg19: chr3-64171993;