rs76335820

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_145239.3(PRRT2):c.647C>A(p.Pro216His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000369 in 1,582,356 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P216R) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00038 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00037 ( 3 hom. )

Consequence

PRRT2
NM_145239.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.28

Publications

25 publications found

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:

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

MVP-DT links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.010031402).

BP6

Variant 16-29813701-C-A is Benign according to our data. Variant chr16-29813701-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 206689.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 3 AD,AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145239.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PRRT2	NM_145239.3	MANE Select	c.647C>A	p.Pro216His	missense	Exon 2 of 4	NP_660282.2	Q7Z6L0-1
PRRT2	NM_001256442.2		c.647C>A	p.Pro216His	missense	Exon 2 of 3	NP_001243371.1	Q7Z6L0-2
PRRT2	NM_001438121.1		c.647C>A	p.Pro216His	missense	Exon 2 of 3	NP_001425050.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PRRT2	ENST00000358758.12	TSL:1 MANE Select	c.647C>A	p.Pro216His	missense	Exon 2 of 4	ENSP00000351608.7	Q7Z6L0-1
ENSG00000280893	ENST00000609618.2	TSL:5	n.647C>A		non_coding_transcript_exon	Exon 2 of 6	ENSP00000476774.2	A0A0G2JLL6
PRRT2	ENST00000567659.3	TSL:2	c.647C>A	p.Pro216His	missense	Exon 2 of 3	ENSP00000456226.1	Q7Z6L0-2

Frequencies

GnomAD3 genomes

AF:

0.000382

AC:

AN:

151936

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00692

Gnomad EAS

AF:

0.00116

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.0000945

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000235

Gnomad OTH

AF:

0.00144

GnomAD2 exomes

AF:

0.000506

AC:

110

AN:

217286

AF XY:

0.000558

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000653

Gnomad ASJ exome

AF:

0.00616

Gnomad EAS exome

AF:

0.000518

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000165

Gnomad OTH exome

AF:

0.000772

GnomAD4 exome

AF:

0.000368

AC:

526

AN:

1430300

Hom.:

Cov.:

AF XY:

0.000433

AC XY:

307

AN XY:

709434

show subpopulations

African (AFR)

AF:

0.0000310

AC:

AN:

32310

American (AMR)

AF:

0.0000489

AC:

AN:

40930

Ashkenazi Jewish (ASJ)

AF:

0.00825

AC:

198

AN:

24002

East Asian (EAS)

AF:

0.000230

AC:

AN:

39172

South Asian (SAS)

AF:

0.00131

AC:

107

AN:

81992

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51922

Middle Eastern (MID)

AF:

0.00107

AC:

AN:

5612

European-Non Finnish (NFE)

AF:

0.000154

AC:

169

AN:

1095536

Other (OTH)

AF:

0.000578

AC:

AN:

58824

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.596

Heterozygous variant carriers

103

129

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.000381

AC:

AN:

152056

Hom.:

Cov.:

AF XY:

0.000404

AC XY:

AN XY:

74328

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41500

American (AMR)

AF:

0.00

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00692

AC:

AN:

3468

East Asian (EAS)

AF:

0.00117

AC:

AN:

5142

South Asian (SAS)

AF:

0.00145

AC:

AN:

4812

European-Finnish (FIN)

AF:

0.0000945

AC:

AN:

10584

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000235

AC:

AN:

67950

Other (OTH)

AF:

0.00142

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.539

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.000772

Hom.:

Bravo

AF:

0.000287

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ExAC

AF:

0.000372

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Episodic kinesigenic dyskinesia (1)

Inborn genetic diseases (1)

not provided (1)

not specified (1)

PRRT2-related disorder (1)

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

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Uncertain

-0.040

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.028

Eigen

Uncertain

0.26

Eigen_PC

Benign

0.21

FATHMM_MKL

Benign

0.65

LIST_S2

Benign

0.70

M_CAP

Uncertain

0.17

MetaRNN

Benign

0.010

MetaSVM

Uncertain

0.58

MutationAssessor

Benign

0.90

PhyloP100

2.3

PrimateAI

Uncertain

0.56

PROVEAN

Benign

1.0

REVEL

Uncertain

0.37

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.030

Polyphen

1.0

Vest4

0.30

MutPred

0.19

Gain of helix (P = 0.0022)

MVP

0.98

MPC

0.93

ClinPred

0.043

GERP RS

3.9

Varity_R

0.27

gMVP

0.32

Mutation Taster

=89/11

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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