Genetic Variant PRRT2:c.-65-28_-65-7dupACCCCAAGCCTATCTCCTCCTC (chr16-29812954-C-CCCTCCTCACCCCAAGCCTATCT) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_145239.3(PRRT2):c.-65-28_-65-7dupACCCCAAGCCTATCTCCTCCTC variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,126 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000017 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PRRT2
NM_145239.3 splice_region, intron

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.408

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 -2 ACMG points.

BP6

Variant 16-29812954-C-CCCTCCTCACCCCAAGCCTATCT is Benign according to our data. Variant chr16-29812954-C-CCCTCCTCACCCCAAGCCTATCT is described in ClinVar as Likely_benign. ClinVar VariationId is 422999.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	Effect	Exon Rank	Protein	UniProt
PRRT2	NM_145239.3	MANE Select	c.-65-28_-65-7dupACCCCAAGCCTATCTCCTCCTC	splice_region intron	N/A	NP_660282.2	Q7Z6L0-1
PRRT2	NM_001256442.2		c.-65-28_-65-7dupACCCCAAGCCTATCTCCTCCTC	splice_region intron	N/A	NP_001243371.1	Q7Z6L0-2
PRRT2	NM_001438121.1		c.-65-28_-65-7dupACCCCAAGCCTATCTCCTCCTC	splice_region intron	N/A	NP_001425050.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PRRT2	ENST00000358758.12	TSL:1 MANE Select	c.-65-36_-65-35insCCTCCTCACCCCAAGCCTATCT	intron	N/A	ENSP00000351608.7	Q7Z6L0-1
ENSG00000280893	ENST00000609618.2	TSL:5	n.-65-36_-65-35insCCTCCTCACCCCAAGCCTATCT	intron	N/A	ENSP00000476774.2	A0A0G2JLL6
PRRT2	ENST00000567659.3	TSL:2	c.-65-36_-65-35insCCTCCTCACCCCAAGCCTATCT	intron	N/A	ENSP00000456226.1	Q7Z6L0-2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152126

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000170

AC:

AN:

1177682

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

585102

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26392

American (AMR)

AF:

0.00

AC:

AN:

28840

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18746

East Asian (EAS)

AF:

0.00

AC:

AN:

38024

South Asian (SAS)

AF:

0.00

AC:

AN:

65830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47640

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3552

European-Non Finnish (NFE)

AF:

0.00000223

AC:

AN:

898808

Other (OTH)

AF:

0.00

AC:

AN:

49850

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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:

0.00000657

AC:

AN:

152126

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74316

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41412

American (AMR)

AF:

0.00

AC:

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68020

Other (OTH)

AF:

0.00

AC:

AN:

2092

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

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.41

Splicing

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over