Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_145239.3(PRRT2):c.364C>A(p.Gln122Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 31)

Consequence

PRRT2
NM_145239.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0750

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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08237946).

BP6

Variant 16-29813418-C-A is Benign according to our data. Variant chr16-29813418-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 468614.Status of the report is criteria_provided_single_submitter, 1 stars.

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.364C>A	p.Gln122Lys	missense	Exon 2 of 4	NP_660282.2
PRRT2	NM_001256442.2		c.364C>A	p.Gln122Lys	missense	Exon 2 of 3	NP_001243371.1
PRRT2	NM_001438121.1		c.364C>A	p.Gln122Lys	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.364C>A	p.Gln122Lys	missense	Exon 2 of 4	ENSP00000351608.7
ENSG00000280893	ENST00000609618.2	TSL:5	n.364C>A		non_coding_transcript_exon	Exon 2 of 6	ENSP00000476774.2
PRRT2	ENST00000567659.3	TSL:2	c.364C>A	p.Gln122Lys	missense	Exon 2 of 3	ENSP00000456226.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions as Germline

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Episodic kinesigenic dyskinesia (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.42

CADD

Benign

(source)

DANN

Benign

0.91

DEOGEN2

Benign

0.0097

Eigen

Benign

-0.62

Eigen_PC

Benign

-0.57

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.60

M_CAP

Benign

0.028

MetaRNN

Benign

0.082

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.8

PhyloP100

0.075

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.30

REVEL

Benign

0.025

Sift

Uncertain

0.0050

Sift4G

Benign

0.56

Polyphen

0.035

Vest4

0.16

MutPred

0.21

Gain of ubiquitination at Q122 (P = 0.0069)

MVP

0.84

MPC

0.47

ClinPred

0.11

GERP RS

2.2

Varity_R

0.074

gMVP

0.053

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

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rs1555502665

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over