rs200926711

Positions:

chr16-29813698-C-G

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_145239.3(PRRT2):c.644C>G(p.Pro215Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000393 in 1,575,196 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00046 ( 1 hom., cov: 31)

Exomes 𝑓: 0.00039 ( 5 hom. )

Consequence

PRRT2
NM_145239.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.721

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:

ENSG00000280893 (HGNC:):

ENSG00000280893 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004953712).

BP6

Variant 16-29813698-C-G is Benign according to our data. Variant chr16-29813698-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 206688.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-29813698-C-G is described in Lovd as [Benign]. Variant chr16-29813698-C-G is described in Lovd as [Likely_benign].

BS2

High AC in GnomAd4 at 70 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRRT2	NM_145239.3 linkuse as main transcript	c.644C>G	p.Pro215Arg	missense_variant	2/4	ENST00000358758.12	NP_660282.2	Q7Z6L0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRRT2	ENST00000358758.12 linkuse as main transcript	c.644C>G	p.Pro215Arg	missense_variant	2/4	1	NM_145239.3	ENSP00000351608.7		Q7Z6L0-1
ENSG00000280893	ENST00000609618.2 linkuse as main transcript	n.644C>G		non_coding_transcript_exon_variant	2/6	5		ENSP00000476774.2		A0A0G2JLL6

Frequencies

GnomAD3 genomes

AF:

0.000468

AC:

AN:

151636

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000726

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00230

Gnomad ASJ

AF:

0.00317

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00272

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000844

AC:

183

AN:

216884

Hom.:

AF XY:

0.00107

AC XY:

126

AN XY:

118062

show subpopulations

Gnomad AFR exome

AF:

0.0000723

Gnomad AMR exome

AF:

0.00104

Gnomad ASJ exome

AF:

0.00577

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00289

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000299

Gnomad OTH exome

AF:

0.000774

GnomAD4 exome

AF:

0.000386

AC:

549

AN:

1423432

Hom.:

Cov.:

AF XY:

0.000510

AC XY:

360

AN XY:

706426

show subpopulations

Gnomad4 AFR exome

AF:

0.0000311

Gnomad4 AMR exome

AF:

0.00103

Gnomad4 ASJ exome

AF:

0.00500

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00230

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000115

Gnomad4 OTH exome

AF:

0.000700

GnomAD4 genome

AF:

0.000461

AC:

AN:

151764

Hom.:

Cov.:

AF XY:

0.000553

AC XY:

AN XY:

74192

show subpopulations

Gnomad4 AFR

AF:

0.0000724

Gnomad4 AMR

AF:

0.00229

Gnomad4 ASJ

AF:

0.00317

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00251

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.000811

Hom.:

Bravo

AF:

0.000706

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000471

AC:

ExAC

AF:

0.000769

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 28, 2019	This variant is associated with the following publications: (PMID: 23077024, 22243967, 23566103, 31124310, 24594579) -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jul 01, 2024	PRRT2: BS2 -

Episodic kinesigenic dyskinesia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 15, 2024

- -

Inborn genetic diseases

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

May 02, 2018

This alteration is classified as likely 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. -

Seizures, benign familial infantile, 2;C1865926:Infantile convulsions and choreoathetosis;C4552000:Episodic kinesigenic dyskinesia 1

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Oct 12, 2021

- -

PRRT2-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 23, 2020

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.20

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.13

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

Eigen

Uncertain

0.32

Eigen_PC

Uncertain

0.28

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.78

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

M_CAP

Benign

0.031

MetaRNN

Benign

0.0050

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

MetaSVM

Benign

-0.39

MutationAssessor

Benign

0.90

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

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-0.11

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

REVEL

Benign

0.22

Sift

Uncertain

0.0080

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

Sift4G

Uncertain

0.048

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

Polyphen

1.0

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

Vest4

0.27

MVP

0.94

MPC

0.90

ClinPred

0.022

GERP RS

2.9

Varity_R

0.075

gMVP

0.33

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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