chr3-64354961-A-C

Variant names:

• chr3-64354961-A-C
• rs9812599
• ENST00000295902.11:c.128+89522T>G

Variant summary

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

The ENST00000295902.11(PRICKLE2):​c.128+89522T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.182 in 152,194 control chromosomes in the GnomAD database, including 2,542 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 0.18 (2542 hom., cov: 32)
• Consequence: PRICKLE2 ENST00000295902.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.07
• 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=-0.74).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.205 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRICKLE2	ENST00000295902.11	c.128+89522T>G		intron_variant	Intron 2 of 8	5		ENSP00000295902.7
PRICKLE2	ENST00000498162.2	c.107+89522T>G		intron_variant	Intron 2 of 4	5		ENSP00000419951.2
PRICKLE2	ENST00000485770.2	n.340+89522T>G		intron_variant	Intron 2 of 3	5

Frequencies

GnomAD3 genomes AF: 0.182 AC: 27620 AN: 152076 Hom.: 2537 Cov.: 32

Gnomad AFR AF: 0.208

Gnomad AMI AF: 0.136

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.125

Gnomad EAS AF: 0.212

Gnomad SAS AF: 0.213

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.174

Gnomad OTH AF: 0.171

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

GnomAD4 genome AF: 0.182 AC: 27656 AN: 152194 Hom.: 2542 Cov.: 32 AF XY: 0.182 AC XY: 13539 AN XY: 74410

African (AFR) AF: 0.208 AC: 8645 AN: 41520

American (AMR) AF: 0.183 AC: 2795 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.125 AC: 433 AN: 3472

East Asian (EAS) AF: 0.213 AC: 1098 AN: 5162

South Asian (SAS) AF: 0.212 AC: 1020 AN: 4820

European-Finnish (FIN) AF: 0.123 AC: 1299 AN: 10602

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.174 AC: 11835 AN: 68000

Other (OTH) AF: 0.170 AC: 359 AN: 2116

Alfa AF: 0.160 Hom.: 1116

Bravo AF: 0.187

Asia WGS AF: 0.201 AC: 700 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	12
DANN	Benign	0.85
PhyloP100		3.1
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: rs9812599; hg19: chr3-64340637;