3-64094813-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_198859.4(PRICKLE2):c.*4238C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 152,662 control chromosomes in the GnomAD database, including 2,439 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.16 (2433 hom., cov: 33)
  • Exomes 𝑓: 0.20 (6 hom.)
• Consequence: PRICKLE2 NM_198859.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.90

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 3-64094813-G-A is Benign according to our data. Variant chr3-64094813-G-A is described in ClinVar as [Benign]. Clinvar id is 346422.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.218 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRICKLE2	NM_198859.4	c.*4238C>T		3_prime_UTR_variant	8/8	ENST00000638394.2
PRICKLE2-AS1	NR_045697.1	n.199-281G>A		intron_variant, non_coding_transcript_variant
PRICKLE2	NM_001370528.1	c.*4238C>T		3_prime_UTR_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRICKLE2	ENST00000638394.2	c.*4238C>T		3_prime_UTR_variant	8/8	1	NM_198859.4
PRICKLE2-AS1	ENST00000482609.1	n.199-281G>A		intron_variant, non_coding_transcript_variant		1
PRICKLE2	ENST00000295902.11	c.*4238C>T		3_prime_UTR_variant	9/9	5		P1
PRICKLE2	ENST00000564377.6	c.*4238C>T		3_prime_UTR_variant	8/8	5

Frequencies

GnomAD3 genomes AF: 0.158 AC: 23971 AN: 152114 Hom.: 2433 Cov.: 33

Gnomad AFR AF: 0.0581

Gnomad AMI AF: 0.204

Gnomad AMR AF: 0.176

Gnomad ASJ AF: 0.257

Gnomad EAS AF: 0.0214

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.150

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.221

Gnomad OTH AF: 0.186

GnomAD4 exome AF: 0.198 AC: 85 AN: 430 Hom.: 6 Cov.: 0 AF XY: 0.190 AC XY: 49 AN XY: 258

Gnomad4 FIN exome AF: 0.199

Gnomad4 NFE exome AF: 0.250

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.157 AC: 23968 AN: 152232 Hom.: 2433 Cov.: 33 AF XY: 0.152 AC XY: 11325 AN XY: 74438

Gnomad4 AFR AF: 0.0581

Gnomad4 AMR AF: 0.176

Gnomad4 ASJ AF: 0.257

Gnomad4 EAS AF: 0.0214

Gnomad4 SAS AF: 0.128

Gnomad4 FIN AF: 0.150

Gnomad4 NFE AF: 0.221

Gnomad4 OTH AF: 0.184

Alfa AF: 0.211 Hom.: 7366

Bravo AF: 0.157

Asia WGS AF: 0.0740 AC: 259 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Progressive myoclonic epilepsy Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	0.039
Dann	Benign	0.68

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs14056; hg19: chr3-64080489;