rs79182085

Positions:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_145239.3(PRRT2):c.412C>G(p.Pro138Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0078 in 1,613,864 control chromosomes in the GnomAD database, including 688 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0079 ( 55 hom., cov: 31)

Exomes 𝑓: 0.0078 ( 633 hom. )

Consequence

PRRT2
NM_145239.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: 0.229

Variant links:

Genes affected

PRRT2 (HGNC:30500): (proline rich transmembrane protein 2) This gene encodes a transmembrane protein containing a proline-rich domain in its N-terminal half. Studies in mice suggest that it is predominantly expressed in brain and spinal cord in embryonic and postnatal stages. Mutations in this gene are associated with episodic kinesigenic dyskinesia-1. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2012]

PRRT2 links:

MVP-DT (HGNC:56029): (MVP divergent transcript)

MVP-DT links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.001377523).

BP6

Variant 16-29813466-C-G is Benign according to our data. Variant chr16-29813466-C-G is described in ClinVar as [Benign]. Clinvar id is 130038.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-29813466-C-G is described in Lovd as [Benign]. Variant chr16-29813466-C-G is described in Lovd as [Likely_pathogenic].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.094 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRRT2	NM_145239.3 linkuse as main transcript	c.412C>G	p.Pro138Ala	missense_variant	2/4	ENST00000358758.12	NP_660282.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRRT2	ENST00000358758.12 linkuse as main transcript	c.412C>G	p.Pro138Ala	missense_variant	2/4	1	NM_145239.3	ENSP00000351608	P1	Q7Z6L0-1
MVP-DT	ENST00000569039.5 linkuse as main transcript	n.246-3293G>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.00791

AC:

1204

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0264

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.101

Gnomad SAS

AF:

0.0244

Gnomad FIN

AF:

0.00235

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000588

Gnomad OTH

AF:

0.00718

GnomAD3 exomes

AF:

0.0184

AC:

4623

AN:

250670

Hom.:

161

AF XY:

0.0168

AC XY:

2279

AN XY:

135550

show subpopulations

Gnomad AFR exome

AF:

0.00216

Gnomad AMR exome

AF:

0.0606

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0883

Gnomad SAS exome

AF:

0.0228

Gnomad FIN exome

AF:

0.00222

Gnomad NFE exome

AF:

0.000610

Gnomad OTH exome

AF:

0.00964

GnomAD4 exome

AF:

0.00779

AC:

11381

AN:

1461564

Hom.:

633

Cov.:

AF XY:

0.00805

AC XY:

5850

AN XY:

727062

show subpopulations

Gnomad4 AFR exome

AF:

0.00105

Gnomad4 AMR exome

AF:

0.0571

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.146

Gnomad4 SAS exome

AF:

0.0232

Gnomad4 FIN exome

AF:

0.00236

Gnomad4 NFE exome

AF:

0.000353

Gnomad4 OTH exome

AF:

0.00802

GnomAD4 genome

AF:

0.00793

AC:

1208

AN:

152300

Hom.:

Cov.:

AF XY:

0.00923

AC XY:

687

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.00192

Gnomad4 AMR

AF:

0.0265

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.101

Gnomad4 SAS

AF:

0.0240

Gnomad4 FIN

AF:

0.00235

Gnomad4 NFE

AF:

0.000588

Gnomad4 OTH

AF:

0.00805

Alfa

AF:

0.00104

Hom.:

Bravo

AF:

0.0101

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00250

AC:

ESP6500EA

AF:

0.000814

AC:

ExAC

AF:

0.0173

AC:

2100

Asia WGS

AF:

0.0570

AC:

197

AN:

3478

EpiCase

AF:

0.000491

EpiControl

AF:

0.000593

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 21, 2018	This variant is associated with the following publications: (PMID: 23063574, 23496026, 28525812, 23529024, 23436308, 22101681, 23532549, 25522171, 31124310) -
Benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Nov 16, 2016	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Sep 04, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:3

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	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Apr 07, 2014	- -

Episodic kinesigenic dyskinesia 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Mendelics

May 28, 2019

- -

Episodic kinesigenic dyskinesia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Inborn genetic diseases

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 25, 2016

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.063

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Benign

0.84

DEOGEN2

Benign

0.0095

T;.;.;.;.;T;.;T;T

Eigen

Benign

-0.79

Eigen_PC

Benign

-0.75

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.72

.;.;T;T;T;.;T;.;T

MetaRNN

Benign

0.0014

T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

L;L;L;.;L;L;.;L;L

MutationTaster

Benign

0.99

N;N;N

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.33

N;.;N;.;N;.;.;.;.

REVEL

Benign

0.032

Sift

Uncertain

0.022

D;.;D;.;D;.;.;.;.

Sift4G

Uncertain

0.029

D;.;D;.;D;.;.;D;.

Polyphen

0.0010

B;B;B;.;B;B;.;B;B

Vest4

0.19

MPC

0.27

ClinPred

0.00030

GERP RS

-0.30

Varity_R

0.070

gMVP

0.039

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