rs27673

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_198859.4(PRICKLE2):c.816T>C(p.Asp272Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.995 in 1,613,902 control chromosomes in the GnomAD database, including 799,631 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.99 ( 74145 hom., cov: 33)

Exomes 𝑓: 1.0 ( 725486 hom. )

Consequence

PRICKLE2
NM_198859.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -0.979

Publications

14 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 Gene-Disease associations (from GenCC):

complex neurodevelopmental disorder
Inheritance: AD Classification: LIMITED Submitted by: ClinGen
neurodevelopmental disorder
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

PRICKLE2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant 3-64147674-A-G is Benign according to our data. Variant chr3-64147674-A-G is described in ClinVar as Benign. ClinVar VariationId is 130137.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.979 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.991 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRICKLE2	NM_198859.4 link	c.816T>C	p.Asp272Asp	synonymous_variant	Exon 7 of 8	ENST00000638394.2	NP_942559.1
PRICKLE2	NM_001370528.1 link	c.816T>C	p.Asp272Asp	synonymous_variant	Exon 7 of 8		NP_001357457.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRICKLE2	ENST00000638394.2 link	c.816T>C	p.Asp272Asp	synonymous_variant	Exon 7 of 8	1	NM_198859.4	ENSP00000492363.1

Frequencies

GnomAD3 genomes

AF:

0.986

AC:

150138

AN:

152202

Hom.:

74089

Cov.:

show subpopulations

Gnomad AFR

AF:

0.958

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.993

Gnomad ASJ

AF:

1.00

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

1.00

Gnomad FIN

AF:

0.999

Gnomad MID

AF:

1.00

Gnomad NFE

AF:

0.997

Gnomad OTH

AF:

0.989

GnomAD2 exomes

AF:

0.995

AC:

246851

AN:

248062

AF XY:

0.996

show subpopulations

Gnomad AFR exome

AF:

0.954

Gnomad AMR exome

AF:

0.995

Gnomad ASJ exome

AF:

1.00

Gnomad EAS exome

AF:

1.00

Gnomad FIN exome

AF:

0.999

Gnomad NFE exome

AF:

0.998

Gnomad OTH exome

AF:

0.996

GnomAD4 exome

AF:

0.996

AC:

1456230

AN:

1461582

Hom.:

725486

Cov.:

AF XY:

0.997

AC XY:

724608

AN XY:

727106

show subpopulations

African (AFR)

AF:

0.959

AC:

32092

AN:

33478

American (AMR)

AF:

0.995

AC:

44513

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

26136

AN:

26136

East Asian (EAS)

AF:

1.00

AC:

39699

AN:

39700

South Asian (SAS)

AF:

1.00

AC:

86230

AN:

86258

European-Finnish (FIN)

AF:

0.999

AC:

53084

AN:

53128

Middle Eastern (MID)

AF:

0.996

AC:

5746

AN:

5768

European-Non Finnish (NFE)

AF:

0.997

AC:

1108684

AN:

1111994

Other (OTH)

AF:

0.994

AC:

60046

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

330

660

991

1321

1651

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21670

43340

65010

86680

108350

<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:

0.986

AC:

150253

AN:

152320

Hom.:

74145

Cov.:

AF XY:

0.987

AC XY:

73487

AN XY:

74480

show subpopulations

African (AFR)

AF:

0.958

AC:

39806

AN:

41566

American (AMR)

AF:

0.993

AC:

15207

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

3472

AN:

3472

East Asian (EAS)

AF:

1.00

AC:

5160

AN:

5160

South Asian (SAS)

AF:

1.00

AC:

4826

AN:

4826

European-Finnish (FIN)

AF:

0.999

AC:

10616

AN:

10622

Middle Eastern (MID)

AF:

1.00

AC:

294

AN:

294

European-Non Finnish (NFE)

AF:

0.997

AC:

67867

AN:

68040

Other (OTH)

AF:

0.989

AC:

2093

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

110

219

329

438

548

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

914

1828

2742

3656

4570

<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:

0.992

Hom.:

48653

Bravo

AF:

0.985

Asia WGS

AF:

0.998

AC:

3470

AN:

3478

EpiCase

AF:

0.998

EpiControl

AF:

0.998

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Progressive myoclonic epilepsy type 5

Benign:3

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 11, 2016

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not specified

Benign:2

Apr 20, 2018

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

not provided

Benign:2

May 03, 2018

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Progressive myoclonic epilepsy

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

-0.93

CADD

Benign

0.025

(source)

DANN

Benign

0.27

PhyloP100

-0.98

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over