Genetic Variant PRRT2:p.Arg227Pro (chr16-29813734-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_145239.3(PRRT2):c.680G>C(p.Arg227Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000699 in 1,429,710 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R227G) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

PRRT2
NM_145239.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.07

Publications

0 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: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10042736).

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
PRRT2	NM_145239.3	MANE Select	c.680G>C	p.Arg227Pro	missense	Exon 2 of 4	NP_660282.2
PRRT2	NM_001256442.2		c.680G>C	p.Arg227Pro	missense	Exon 2 of 3	NP_001243371.1
PRRT2	NM_001438121.1		c.680G>C	p.Arg227Pro	missense	Exon 2 of 3	NP_001425050.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
PRRT2	ENST00000358758.12	TSL:1 MANE Select	c.680G>C	p.Arg227Pro	missense	Exon 2 of 4	ENSP00000351608.7
ENSG00000280893	ENST00000609618.2	TSL:5	n.680G>C		non_coding_transcript_exon	Exon 2 of 6	ENSP00000476774.2
PRRT2	ENST00000567659.3	TSL:2	c.680G>C	p.Arg227Pro	missense	Exon 2 of 3	ENSP00000456226.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.99e-7

AC:

AN:

1429710

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

708300

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32374

American (AMR)

AF:

0.00

AC:

AN:

40780

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23712

East Asian (EAS)

AF:

0.00

AC:

AN:

39338

South Asian (SAS)

AF:

0.00

AC:

AN:

81532

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51992

Middle Eastern (MID)

AF:

0.000179

AC:

AN:

5582

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1095596

Other (OTH)

AF:

0.00

AC:

AN:

58804

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.36

BayesDel_addAF

Pathogenic

0.22

BayesDel_noAF

Uncertain

0.080

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0082

Eigen

Benign

-0.038

Eigen_PC

Benign

-0.18

FATHMM_MKL

Benign

0.39

LIST_S2

Benign

0.79

M_CAP

Benign

0.033

MetaRNN

Benign

0.10

MetaSVM

Benign

-0.76

MutationAssessor

Benign

0.46

PhyloP100

1.1

PrimateAI

Uncertain

0.50

PROVEAN

Benign

1.5

REVEL

Benign

0.26

Sift

Uncertain

0.0040

Sift4G

Uncertain

0.059

Polyphen

1.0

Vest4

0.24

MutPred

0.23

Loss of MoRF binding (P = 0.0034)

MVP

0.86

MPC

0.47

ClinPred

0.28

GERP RS

2.9

Varity_R

0.22

gMVP

0.36

Mutation Taster

=81/19

polymorphism

(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

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over