dbSNP rs149105: PRICKLE2:c.145-12157A>T (chr3-64175286-T-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_198859.4(PRICKLE2):c.145-12157A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.425 in 152,898 control chromosomes in the GnomAD database, including 14,373 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 0.43 ( 14308 hom., cov: 32)

Exomes 𝑓: 0.38 ( 65 hom. )

Consequence

PRICKLE2
NM_198859.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0990

Publications

3 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:

PRDX3P4 (HGNC:44643): (peroxiredoxin 3 pseudogene 4)

PRDX3P4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.543 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRICKLE2	NM_198859.4	MANE Select	c.145-12157A>T		intron	N/A	NP_942559.1	Q7Z3G6
	PRICKLE2	NM_001370528.1		c.145-12157A>T		intron	N/A	NP_001357457.1	Q7Z3G6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PRICKLE2	ENST00000638394.2	TSL:1 MANE Select	c.145-12157A>T	intron	N/A	ENSP00000492363.1	Q7Z3G6
PRICKLE2	ENST00000295902.11	TSL:5	c.313-12157A>T	intron	N/A	ENSP00000295902.7	A0A1X7SBR1
PRICKLE2	ENST00000906078.1		c.145-12157A>T	intron	N/A	ENSP00000576137.1

Frequencies

GnomAD3 genomes

AF:

0.425

AC:

64481

AN:

151798

Hom.:

14276

Cov.:

show subpopulations

Gnomad AFR

AF:

0.549

Gnomad AMI

AF:

0.366

Gnomad AMR

AF:

0.328

Gnomad ASJ

AF:

0.398

Gnomad EAS

AF:

0.460

Gnomad SAS

AF:

0.396

Gnomad FIN

AF:

0.389

Gnomad MID

AF:

0.379

Gnomad NFE

AF:

0.380

Gnomad OTH

AF:

0.388

GnomAD4 exome

AF:

0.384

AC:

376

AN:

980

Hom.:

AF XY:

0.388

AC XY:

188

AN XY:

484

show subpopulations

African (AFR)

AF:

0.375

AC:

AN:

American (AMR)

AF:

0.300

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

0.600

AC:

AN:

European-Finnish (FIN)

AF:

0.385

AC:

286

AN:

742

Middle Eastern (MID)

AF:

0.333

AC:

AN:

European-Non Finnish (NFE)

AF:

0.358

AC:

AN:

176

Other (OTH)

AF:

0.458

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.425

AC:

64573

AN:

151918

Hom.:

14308

Cov.:

AF XY:

0.423

AC XY:

31423

AN XY:

74256

show subpopulations

African (AFR)

AF:

0.549

AC:

22719

AN:

41374

American (AMR)

AF:

0.328

AC:

5012

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.398

AC:

1382

AN:

3470

East Asian (EAS)

AF:

0.460

AC:

2380

AN:

5174

South Asian (SAS)

AF:

0.397

AC:

1912

AN:

4812

European-Finnish (FIN)

AF:

0.389

AC:

4097

AN:

10540

Middle Eastern (MID)

AF:

0.387

AC:

113

AN:

292

European-Non Finnish (NFE)

AF:

0.380

AC:

25810

AN:

67956

Other (OTH)

AF:

0.387

AC:

815

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1866

3732

5599

7465

9331

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

618

1236

1854

2472

3090

<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:

0.407

Hom.:

1568

Bravo

AF:

0.426

Asia WGS

AF:

0.411

AC:

1432

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.74

(source)

DANN

Benign

0.86

PhyloP100

0.099

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over