Genetic Variant PRICKLE2:c.*4238C>T (chr3-64094813-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.90

Publications

10 publications found

Variant links:

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 links:

PRICKLE2-AS1 (HGNC:):

PRICKLE2-AS1 links:

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

PRICKLE2-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 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 VariationId is 346422.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.218 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198859.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PRICKLE2	NM_198859.4	MANE Select	c.*4238C>T	3_prime_UTR	Exon 8 of 8	NP_942559.1	Q7Z3G6
PRICKLE2	NM_001370528.1		c.*4238C>T	3_prime_UTR	Exon 8 of 8	NP_001357457.1	Q7Z3G6
PRICKLE2-AS1	NR_045697.1		n.199-281G>A	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PRICKLE2	ENST00000638394.2	TSL:1 MANE Select	c.*4238C>T	3_prime_UTR	Exon 8 of 8	ENSP00000492363.1	Q7Z3G6
PRICKLE2-AS1	ENST00000482609.1	TSL:1	n.199-281G>A	intron	N/A
PRICKLE2	ENST00000295902.11	TSL:5	c.*4238C>T	3_prime_UTR	Exon 9 of 9	ENSP00000295902.7	A0A1X7SBR1

Frequencies

GnomAD3 genomes

AF:

0.158

AC:

23971

AN:

152114

Hom.:

2433

Cov.:

show subpopulations

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:

AN:

430

Hom.:

Cov.:

AF XY:

0.190

AC XY:

AN XY:

258

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.199

AC:

AN:

422

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.250

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.441

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.157

AC:

23968

AN:

152232

Hom.:

2433

Cov.:

AF XY:

0.152

AC XY:

11325

AN XY:

74438

show subpopulations

African (AFR)

AF:

0.0581

AC:

2416

AN:

41556

American (AMR)

AF:

0.176

AC:

2693

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.257

AC:

891

AN:

3470

East Asian (EAS)

AF:

0.0214

AC:

111

AN:

5176

South Asian (SAS)

AF:

0.128

AC:

616

AN:

4822

European-Finnish (FIN)

AF:

0.150

AC:

1586

AN:

10602

Middle Eastern (MID)

AF:

0.262

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.221

AC:

15002

AN:

67990

Other (OTH)

AF:

0.184

AC:

390

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1005

2010

3015

4020

5025

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

262

524

786

1048

1310

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.203

Hom.:

14855

Bravo

AF:

0.157

Asia WGS

AF:

0.0740

AC:

259

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Progressive myoclonic epilepsy (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.039

(source)

DANN

Benign

0.68

PhyloP100

-1.9

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over