3-64094318-C-T

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.*4733G>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 0.912 in 152,258 control chromosomes in the GnomAD database, including 64,508 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.91 (64508 hom., cov: 33)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: PRICKLE2 NM_198859.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.02

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=-0.88).
• BP6: Variant 3-64094318-C-T is Benign according to our data. Variant chr3-64094318-C-T is described in ClinVar as [Benign]. Clinvar id is 346417.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.991 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRICKLE2	NM_198859.4	c.*4733G>A		3_prime_UTR_variant	8/8	ENST00000638394.2
PRICKLE2-AS1	NR_045697.1	n.199-776C>T		intron_variant, non_coding_transcript_variant
PRICKLE2	NM_001370528.1	c.*4733G>A		3_prime_UTR_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRICKLE2	ENST00000638394.2	c.*4733G>A		3_prime_UTR_variant	8/8	1	NM_198859.4
PRICKLE2-AS1	ENST00000482609.1	n.199-776C>T		intron_variant, non_coding_transcript_variant		1
PRICKLE2	ENST00000295902.11	c.*4733G>A		3_prime_UTR_variant	9/9	5		P1
PRICKLE2	ENST00000564377.6	c.*4733G>A		3_prime_UTR_variant	8/8	5

Frequencies

GnomAD3 genomes AF: 0.913 AC: 138859 AN: 152136 Hom.: 64485 Cov.: 33

Gnomad AFR AF: 0.720

Gnomad AMI AF: 0.980

Gnomad AMR AF: 0.960

Gnomad ASJ AF: 0.993

Gnomad EAS AF: 0.876

Gnomad SAS AF: 0.984

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.953

Gnomad NFE AF: 0.998

Gnomad OTH AF: 0.932

GnomAD4 exome AF: 0.500 AC: 2 AN: 4 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 2 AN XY: 4

Gnomad4 AFR exome AF: 0.500

GnomAD4 genome AF: 0.912 AC: 138924 AN: 152254 Hom.: 64508 Cov.: 33 AF XY: 0.914 AC XY: 67990 AN XY: 74424

Gnomad4 AFR AF: 0.719

Gnomad4 AMR AF: 0.960

Gnomad4 ASJ AF: 0.993

Gnomad4 EAS AF: 0.877

Gnomad4 SAS AF: 0.984

Gnomad4 FIN AF: 1.00

Gnomad4 NFE AF: 0.998

Gnomad4 OTH AF: 0.933

Alfa AF: 0.975 Hom.: 60438

Bravo AF: 0.899

Asia WGS AF: 0.910 AC: 3165 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	-0.88
Cadd	Benign	3.2
Dann	Benign	0.34

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: rs153732; hg19: chr3-64079994;