rs719775

chr3-64405777-T-Achr3-64405777-T-Cchr3-64405777-T-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRICKLE2	ENST00000295902.11	c.128+38706A>T		intron_variant		5		P1
PRICKLE2	ENST00000498162.2	c.109+38706A>T		intron_variant		5
PRICKLE2	ENST00000485770.2	n.340+38706A>T		intron_variant, non_coding_transcript_variant		5

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

Gnomad4 AFR AF: 0.487

Gnomad4 AMR AF: 0.701

Gnomad4 ASJ AF: 0.797

Gnomad4 EAS AF: 0.995

Gnomad4 SAS AF: 0.802

Gnomad4 FIN AF: 0.790

Gnomad4 NFE AF: 0.814

Gnomad4 OTH AF: 0.741

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	0.59
Dann	Benign	0.72

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs719775; hg19: chr3-64391453;