rs888405

Variant names:

• chr3-64216026-A-G
• rs888405
• NM_198859.4:c.-41+8884T>C

Variant summary

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

The NM_198859.4(PRICKLE2):​c.-41+8884T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.658 in 152,180 control chromosomes in the GnomAD database, including 35,867 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 0.66 (35867 hom., cov: 33)
• Consequence: PRICKLE2 NM_198859.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0350
• Publications: 8 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.794 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRICKLE2	NM_198859.4	c.-41+8884T>C		intron_variant	Intron 1 of 7	ENST00000638394.2	NP_942559.1
PRICKLE2	NM_001370528.1	c.-40-17059T>C		intron_variant	Intron 1 of 7		NP_001357457.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRICKLE2	ENST00000638394.2	c.-41+8884T>C		intron_variant	Intron 1 of 7	1	NM_198859.4	ENSP00000492363.1

Frequencies

GnomAD3 genomes AF: 0.658 AC: 100044 AN: 152062 Hom.: 35856 Cov.: 33

Gnomad AFR AF: 0.350

Gnomad AMI AF: 0.740

Gnomad AMR AF: 0.713

Gnomad ASJ AF: 0.809

Gnomad EAS AF: 0.509

Gnomad SAS AF: 0.758

Gnomad FIN AF: 0.834

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.800

Gnomad OTH AF: 0.693

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

GnomAD4 genome AF: 0.658 AC: 100075 AN: 152180 Hom.: 35867 Cov.: 33 AF XY: 0.662 AC XY: 49232 AN XY: 74390

African (AFR) AF: 0.350 AC: 14511 AN: 41504

American (AMR) AF: 0.713 AC: 10906 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.809 AC: 2810 AN: 3472

East Asian (EAS) AF: 0.508 AC: 2626 AN: 5166

South Asian (SAS) AF: 0.758 AC: 3653 AN: 4822

European-Finnish (FIN) AF: 0.834 AC: 8837 AN: 10592

Middle Eastern (MID) AF: 0.646 AC: 190 AN: 294

European-Non Finnish (NFE) AF: 0.800 AC: 54395 AN: 68010

Other (OTH) AF: 0.699 AC: 1474 AN: 2110

Alfa AF: 0.743 Hom.: 134522

Bravo AF: 0.631

Asia WGS AF: 0.648 AC: 2256 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.1
DANN	Benign	0.57
PhyloP100		0.035
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: rs888405; hg19: chr3-64201702;