chr3-64306961-A-T

Variant names:

• chr3-64306961-A-T
• rs741013
• ENST00000295902.11:c.129-107994T>A

Variant summary

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

The ENST00000295902.11(PRICKLE2):​c.129-107994T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0601 in 152,294 control chromosomes in the GnomAD database, including 358 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 0.060 (358 hom., cov: 32)
• Consequence: PRICKLE2 ENST00000295902.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.69
• Publications: 7 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=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0864 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRICKLE2	ENST00000295902.11	TSL:5	c.129-107994T>A		intron	N/A	ENSP00000295902.7	A0A1X7SBR1
	PRICKLE2	ENST00000498162.2	TSL:5	c.108-107994T>A		intron	N/A	ENSP00000419951.2	C9JY03
	PRICKLE2	ENST00000485770.2	TSL:5	n.341-107994T>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0601 AC: 9149 AN: 152176 Hom.: 358 Cov.: 32

Gnomad AFR AF: 0.0218

Gnomad AMI AF: 0.0373

Gnomad AMR AF: 0.0647

Gnomad ASJ AF: 0.0982

Gnomad EAS AF: 0.00308

Gnomad SAS AF: 0.0934

Gnomad FIN AF: 0.0662

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0817

Gnomad OTH AF: 0.0669

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

GnomAD4 genome AF: 0.0601 AC: 9152 AN: 152294 Hom.: 358 Cov.: 32 AF XY: 0.0603 AC XY: 4493 AN XY: 74460

African (AFR) AF: 0.0218 AC: 905 AN: 41564

American (AMR) AF: 0.0646 AC: 988 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0982 AC: 341 AN: 3472

East Asian (EAS) AF: 0.00309 AC: 16 AN: 5184

South Asian (SAS) AF: 0.0935 AC: 451 AN: 4824

European-Finnish (FIN) AF: 0.0662 AC: 703 AN: 10614

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0816 AC: 5554 AN: 68024

Other (OTH) AF: 0.0685 AC: 145 AN: 2116

Alfa AF: 0.0701 Hom.: 46

Bravo AF: 0.0571

Asia WGS AF: 0.0600 AC: 209 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.1
DANN	Benign	0.65
PhyloP100		1.7
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: rs741013; hg19: chr3-64292637;