rs1437924015

Variant names:

• chr16-29813705-A-G
• rs1437924015
• NM_145239.3:c.651A>G
• PRRT2 p.Arg217Arg

Your query was ambiguous. Multiple possible variants found:

• chr16-29813705-A-G
• chr16-29813705-A-C
• chr16-29813705-A-T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 2P and 13B. PM2 BP4_Strong BP6_Very_Strong BP7

The NM_145239.3(PRRT2):​c.651A>G​(p.Arg217Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000144 in 139,076 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. R217R) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.000014 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000038 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PRRT2 NM_145239.3 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -5.17
• Publications: 0 publications found

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]

ENSG00000280893 (HGNC:):

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

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 16-29813705-A-G is Benign according to our data. Variant chr16-29813705-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 1085829.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-5.17 with no splicing effect.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRRT2	NM_145239.3	MANE Select	c.651A>G	p.Arg217Arg	synonymous	Exon 2 of 4	NP_660282.2	Q7Z6L0-1
	PRRT2	NM_001256442.2		c.651A>G	p.Arg217Arg	synonymous	Exon 2 of 3	NP_001243371.1	Q7Z6L0-2
	PRRT2	NM_001438121.1		c.651A>G	p.Arg217Arg	synonymous	Exon 2 of 3	NP_001425050.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRRT2	ENST00000358758.12	TSL:1 MANE Select	c.651A>G	p.Arg217Arg	synonymous	Exon 2 of 4	ENSP00000351608.7	Q7Z6L0-1
	ENSG00000280893	ENST00000609618.2	TSL:5	n.651A>G		non_coding_transcript_exon	Exon 2 of 6	ENSP00000476774.2	A0A0G2JLL6
	PRRT2	ENST00000567659.3	TSL:2	c.651A>G	p.Arg217Arg	synonymous	Exon 2 of 3	ENSP00000456226.1	Q7Z6L0-2

Frequencies

GnomAD3 genomes AF: 0.0000144 AC: 2 AN: 139076 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000141

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

GnomAD2 exomes AF: 0.00000939 AC: 2 AN: 212910 AF XY: 0.00000865

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000668

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000376 AC: 3 AN: 798908 Hom.: 0 Cov.: 31 AF XY: 0.00000245 AC XY: 1 AN XY: 407504

African (AFR) AF: 0.00 AC: 0 AN: 17718

American (AMR) AF: 0.0000601 AC: 2 AN: 33290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13004

East Asian (EAS) AF: 0.00 AC: 0 AN: 16500

South Asian (SAS) AF: 0.00 AC: 0 AN: 70518

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32636

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3400

European-Non Finnish (NFE) AF: 0.00000172 AC: 1 AN: 581512

Other (OTH) AF: 0.00 AC: 0 AN: 30330

GnomAD4 genome AF: 0.0000144 AC: 2 AN: 139076 Hom.: 0 Cov.: 31 AF XY: 0.0000148 AC XY: 1 AN XY: 67350

African (AFR) AF: 0.00 AC: 0 AN: 38542

American (AMR) AF: 0.000141 AC: 2 AN: 14182

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3300

East Asian (EAS) AF: 0.00 AC: 0 AN: 3914

South Asian (SAS) AF: 0.00 AC: 0 AN: 3744

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8590

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 302

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 63676

Other (OTH) AF: 0.00 AC: 0 AN: 1970

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Episodic kinesigenic dyskinesia (1)
-	-	1	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.13
DANN	Benign	0.67
PhyloP100		-5.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1437924015;

hg19: chr16-29825026;