Genetic Variant PRRT2:p.Ala214Ala (chr16-29813696-C-T) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_StrongBP7

The NM_145239.3(PRRT2):c.642C>T(p.Ala214Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000046 in 1,520,482 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. Synonymous variant affecting the same amino acid position (i.e. A214A) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0000067 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000044 ( 0 hom. )

Consequence

PRRT2
NM_145239.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.82

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: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.49).

BP7

Synonymous conserved (PhyloP=-1.83 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRRT2	NM_145239.3 link	c.642C>T	p.Ala214Ala	synonymous_variant	Exon 2 of 4	ENST00000358758.12	NP_660282.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRRT2	ENST00000358758.12 link	c.642C>T	p.Ala214Ala	synonymous_variant	Exon 2 of 4	1	NM_145239.3	ENSP00000351608.7
ENSG00000280893	ENST00000609618.2 link	n.642C>T		non_coding_transcript_exon_variant	Exon 2 of 6	5		ENSP00000476774.2

Frequencies

GnomAD3 genomes

AF:

0.00000666

AC:

AN:

150116

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000244

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000438

AC:

AN:

1370366

Hom.:

Cov.:

AF XY:

0.00000440

AC XY:

AN XY:

681698

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30720

American (AMR)

AF:

0.00

AC:

AN:

40092

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22494

East Asian (EAS)

AF:

0.00

AC:

AN:

34676

South Asian (SAS)

AF:

0.00

AC:

AN:

81172

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48584

Middle Eastern (MID)

AF:

0.000184

AC:

AN:

5440

European-Non Finnish (NFE)

AF:

0.00000475

AC:

AN:

1051652

Other (OTH)

AF:

0.00

AC:

AN:

55536

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.533

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

AF:

0.00000666

AC:

AN:

150116

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73258

show subpopulations

African (AFR)

AF:

0.0000244

AC:

AN:

40982

American (AMR)

AF:

0.00

AC:

AN:

15074

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3452

East Asian (EAS)

AF:

0.00

AC:

AN:

4958

South Asian (SAS)

AF:

0.00

AC:

AN:

4646

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10288

Middle Eastern (MID)

AF:

0.00

AC:

AN:

312

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67426

Other (OTH)

AF:

0.00

AC:

AN:

2070

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_noAF

Benign

-0.49

CADD

Benign

4.9

(source)

DANN

Benign

0.78

PhyloP100

-1.8

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over