3-64092333-C-T

Position:

• chr3-64092333-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000638394.2(PRICKLE2):​c.*6718G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.719 in 152,128 control chromosomes in the GnomAD database, including 40,242 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 (40242 hom., cov: 33)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: PRICKLE2 ENST00000638394.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.328

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-AS1 (HGNC:40916): (PRICKLE2 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.826 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRICKLE2	NM_198859.4	c.*6718G>A		3_prime_UTR_variant	8/8	ENST00000638394.2	NP_942559.1
PRICKLE2-AS1	NR_045697.1	n.199-2761C>T		intron_variant, non_coding_transcript_variant
PRICKLE2	NM_001370528.1	c.*6718G>A		3_prime_UTR_variant	8/8		NP_001357457.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRICKLE2	ENST00000638394.2	c.*6718G>A		3_prime_UTR_variant	8/8	1	NM_198859.4	ENSP00000492363
PRICKLE2-AS1	ENST00000482609.1	n.199-2761C>T		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.719 AC: 109329 AN: 152008 Hom.: 40223 Cov.: 33

Gnomad AFR AF: 0.563

Gnomad AMI AF: 0.790

Gnomad AMR AF: 0.838

Gnomad ASJ AF: 0.828

Gnomad EAS AF: 0.573

Gnomad SAS AF: 0.769

Gnomad FIN AF: 0.709

Gnomad MID AF: 0.797

Gnomad NFE AF: 0.789

Gnomad OTH AF: 0.743

GnomAD4 exome AF: 0.500 AC: 1 AN: 2 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

Gnomad4 FIN exome AF: 0.500

GnomAD4 genome AF: 0.719 AC: 109391 AN: 152126 Hom.: 40242 Cov.: 33 AF XY: 0.715 AC XY: 53179 AN XY: 74362

Gnomad4 AFR AF: 0.563

Gnomad4 AMR AF: 0.838

Gnomad4 ASJ AF: 0.828

Gnomad4 EAS AF: 0.573

Gnomad4 SAS AF: 0.769

Gnomad4 FIN AF: 0.709

Gnomad4 NFE AF: 0.789

Gnomad4 OTH AF: 0.747

Alfa AF: 0.785 Hom.: 78926

Bravo AF: 0.723

Asia WGS AF: 0.662 AC: 2304 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.44
DANN	Benign	0.37

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs153734; hg19: chr3-64078009;