chr3-64157183-C-T

Position:

chr3-64157183-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_198859.4(PRICKLE2):c.579G>A(p.Pro193Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.223 in 1,613,502 control chromosomes in the GnomAD database, including 42,307 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 4464 hom., cov: 33)

Exomes 𝑓: 0.22 ( 37843 hom. )

Consequence

PRICKLE2
NM_198859.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -3.71

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 (HGNC:):

PRICKLE2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

BP6

Variant 3-64157183-C-T is Benign according to our data. Variant chr3-64157183-C-T is described in ClinVar as [Benign]. Clinvar id is 130034.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-64157183-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-3.71 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.27 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRICKLE2	NM_198859.4 linkuse as main transcript	c.579G>A	p.Pro193Pro	synonymous_variant	5/8	ENST00000638394.2	NP_942559.1	Q7Z3G6A1LQZ3
PRICKLE2	NM_001370528.1 linkuse as main transcript	c.579G>A	p.Pro193Pro	synonymous_variant	5/8		NP_001357457.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PRICKLE2	ENST00000638394.2 linkuse as main transcript	c.579G>A	p.Pro193Pro	synonymous_variant	5/8	1	NM_198859.4	ENSP00000492363.1	Q7Z3G6
PRICKLE2	ENST00000295902.11 linkuse as main transcript	c.747G>A	p.Pro249Pro	synonymous_variant	6/9	5		ENSP00000295902.7	A0A1X7SBR1
PRICKLE2	ENST00000564377.6 linkuse as main transcript	c.579G>A	p.Pro193Pro	synonymous_variant	5/8	5		ENSP00000455004.2	Q7Z3G6
PRICKLE2	ENST00000640303.1 linkuse as main transcript	n.1218G>A		non_coding_transcript_exon_variant	3/6	5

Frequencies

GnomAD3 genomes

AF:

0.234

AC:

35551

AN:

152072

Hom.:

4457

Cov.:

show subpopulations

Gnomad AFR

AF:

0.274

Gnomad AMI

AF:

0.170

Gnomad AMR

AF:

0.158

Gnomad ASJ

AF:

0.222

Gnomad EAS

AF:

0.00827

Gnomad SAS

AF:

0.176

Gnomad FIN

AF:

0.319

Gnomad MID

AF:

0.123

Gnomad NFE

AF:

0.238

Gnomad OTH

AF:

0.187

GnomAD3 exomes

AF:

0.200

AC:

50179

AN:

250800

Hom.:

5905

AF XY:

0.203

AC XY:

27468

AN XY:

135604

show subpopulations

Gnomad AFR exome

AF:

0.272

Gnomad AMR exome

AF:

0.107

Gnomad ASJ exome

AF:

0.224

Gnomad EAS exome

AF:

0.00577

Gnomad SAS exome

AF:

0.181

Gnomad FIN exome

AF:

0.310

Gnomad NFE exome

AF:

0.232

Gnomad OTH exome

AF:

0.199

GnomAD4 exome

AF:

0.222

AC:

324054

AN:

1461312

Hom.:

37843

Cov.:

AF XY:

0.222

AC XY:

161256

AN XY:

726992

show subpopulations

Gnomad4 AFR exome

AF:

0.278

Gnomad4 AMR exome

AF:

0.112

Gnomad4 ASJ exome

AF:

0.222

Gnomad4 EAS exome

AF:

0.00652

Gnomad4 SAS exome

AF:

0.180

Gnomad4 FIN exome

AF:

0.305

Gnomad4 NFE exome

AF:

0.232

Gnomad4 OTH exome

AF:

0.211

GnomAD4 genome

AF:

0.234

AC:

35607

AN:

152190

Hom.:

4464

Cov.:

AF XY:

0.235

AC XY:

17502

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.274

Gnomad4 AMR

AF:

0.158

Gnomad4 ASJ

AF:

0.222

Gnomad4 EAS

AF:

0.00829

Gnomad4 SAS

AF:

0.176

Gnomad4 FIN

AF:

0.319

Gnomad4 NFE

AF:

0.238

Gnomad4 OTH

AF:

0.190

Alfa

AF:

0.228

Hom.:

8141

Bravo

AF:

0.221

Asia WGS

AF:

0.119

AC:

417

AN:

3478

EpiCase

AF:

0.224

EpiControl

AF:

0.222

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 26, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	May 07, 2018	- -

not specified

Benign:2

Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	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. -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Mar 14, 2014	- -

Progressive myoclonic epilepsy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 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. -

Progressive myoclonic epilepsy type 5

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

0.017

DANN

Benign

0.65

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over