3-64405777-T-A

Variant names:

• chr3-64405777-T-A
• rs719775
• ENST00000295902.11:c.128+38706A>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+38706A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.717 in 152,130 control chromosomes in the GnomAD database, including 40,909 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 0.72 (40909 hom., cov: 33)
• Consequence: PRICKLE2 ENST00000295902.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.313
• Publications: 4 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 (EAS) allele frequency at 95% confidence interval = 0.972 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

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRICKLE2	ENST00000295902.11	TSL:5	c.128+38706A>T		intron	N/A	ENSP00000295902.7
	PRICKLE2	ENST00000498162.2	TSL:5	c.107+38706A>T		intron	N/A	ENSP00000419951.2
	PRICKLE2	ENST00000485770.2	TSL:5	n.340+38706A>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.717 AC: 109023 AN: 152012 Hom.: 40898 Cov.: 33

Gnomad AFR AF: 0.487

Gnomad AMI AF: 0.923

Gnomad AMR AF: 0.702

Gnomad ASJ AF: 0.797

Gnomad EAS AF: 0.995

Gnomad SAS AF: 0.802

Gnomad FIN AF: 0.790

Gnomad MID AF: 0.829

Gnomad NFE AF: 0.814

Gnomad OTH AF: 0.738

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

GnomAD4 genome AF: 0.717 AC: 109073 AN: 152130 Hom.: 40909 Cov.: 33 AF XY: 0.717 AC XY: 53328 AN XY: 74368

African (AFR) AF: 0.487 AC: 20196 AN: 41454

American (AMR) AF: 0.701 AC: 10719 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.797 AC: 2768 AN: 3472

East Asian (EAS) AF: 0.995 AC: 5149 AN: 5174

South Asian (SAS) AF: 0.802 AC: 3857 AN: 4812

European-Finnish (FIN) AF: 0.790 AC: 8376 AN: 10598

Middle Eastern (MID) AF: 0.823 AC: 242 AN: 294

European-Non Finnish (NFE) AF: 0.814 AC: 55360 AN: 68012

Other (OTH) AF: 0.741 AC: 1564 AN: 2112

Alfa AF: 0.756 Hom.: 5551

Bravo AF: 0.699

Asia WGS AF: 0.847 AC: 2945 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.59
DANN	Benign	0.72
PhyloP100		-0.31
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: rs719775; hg19: chr3-64391453;