rs4688187

Variant names:

• chr3-64386931-G-A
• rs4688187
• ENST00000295902.11:c.128+57552C>T

Variant summary

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

The ENST00000295902.11(PRICKLE2):​c.128+57552C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.536 in 152,060 control chromosomes in the GnomAD database, including 25,139 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 0.54 (25139 hom., cov: 33)
• Consequence: PRICKLE2 ENST00000295902.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.172
• Publications: 1 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.836 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000295902.11. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRICKLE2	ENST00000295902.11	TSL:5	c.128+57552C>T		intron	N/A	ENSP00000295902.7
	PRICKLE2	ENST00000498162.2	TSL:5	c.107+57552C>T		intron	N/A	ENSP00000419951.2
	PRICKLE2	ENST00000485770.2	TSL:5	n.340+57552C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.535 AC: 81340 AN: 151942 Hom.: 25087 Cov.: 33

Gnomad AFR AF: 0.823

Gnomad AMI AF: 0.230

Gnomad AMR AF: 0.524

Gnomad ASJ AF: 0.377

Gnomad EAS AF: 0.858

Gnomad SAS AF: 0.565

Gnomad FIN AF: 0.492

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.356

Gnomad OTH AF: 0.504

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

GnomAD4 genome AF: 0.536 AC: 81453 AN: 152060 Hom.: 25139 Cov.: 33 AF XY: 0.546 AC XY: 40586 AN XY: 74334

African (AFR) AF: 0.823 AC: 34185 AN: 41538

American (AMR) AF: 0.524 AC: 8001 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.377 AC: 1309 AN: 3470

East Asian (EAS) AF: 0.857 AC: 4428 AN: 5164

South Asian (SAS) AF: 0.566 AC: 2728 AN: 4820

European-Finnish (FIN) AF: 0.492 AC: 5181 AN: 10536

Middle Eastern (MID) AF: 0.480 AC: 141 AN: 294

European-Non Finnish (NFE) AF: 0.356 AC: 24219 AN: 67950

Other (OTH) AF: 0.499 AC: 1052 AN: 2110

Alfa AF: 0.429 Hom.: 8303

Bravo AF: 0.553

Asia WGS AF: 0.690 AC: 2395 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.77
DANN	Benign	0.70
PhyloP100		-0.17
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs4688187; hg19: chr3-64372607; COSMIC: COSV73860787;