rs149260055

Variant names:

• chr16-29813666-C-G
• rs149260055
• NM_145239.3:c.612C>G

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_145239.3(PRRT2):​c.612C>G​(p.Pro204Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000203 in 1,608,984 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0012 (2 hom., cov: 31)
  • Exomes 𝑓: 0.000098 (0 hom.)
• Consequence: PRRT2 NM_145239.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.690
• 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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP6: Variant 16-29813666-C-G is Benign according to our data. Variant chr16-29813666-C-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 138814.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.69 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 2 AD,AR gene

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.612C>G	p.Pro204Pro	synonymous	Exon 2 of 4	NP_660282.2	Q7Z6L0-1
	PRRT2	NM_001256442.2		c.612C>G	p.Pro204Pro	synonymous	Exon 2 of 3	NP_001243371.1	Q7Z6L0-2
	PRRT2	NM_001438121.1		c.612C>G	p.Pro204Pro	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.612C>G	p.Pro204Pro	synonymous	Exon 2 of 4	ENSP00000351608.7	Q7Z6L0-1
	ENSG00000280893	ENST00000609618.2	TSL:5	n.612C>G		non_coding_transcript_exon	Exon 2 of 6	ENSP00000476774.2	A0A0G2JLL6
	PRRT2	ENST00000567659.3	TSL:2	c.612C>G	p.Pro204Pro	synonymous	Exon 2 of 3	ENSP00000456226.1	Q7Z6L0-2

Frequencies

GnomAD3 genomes AF: 0.00121 AC: 184 AN: 152102 Hom.: 2 Cov.: 31

Gnomad AFR AF: 0.00425

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

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: 0.00143

GnomAD2 exomes AF: 0.000298 AC: 72 AN: 241812 AF XY: 0.000212

Gnomad AFR exome AF: 0.00402

Gnomad AMR exome AF: 0.000358

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 AF: 0.0000982 AC: 143 AN: 1456764 Hom.: 0 Cov.: 32 AF XY: 0.0000704 AC XY: 51 AN XY: 724400

African (AFR) AF: 0.00349 AC: 116 AN: 33226

American (AMR) AF: 0.000296 AC: 13 AN: 43972

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25950

East Asian (EAS) AF: 0.00 AC: 0 AN: 39564

South Asian (SAS) AF: 0.00 AC: 0 AN: 85868

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52850

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5752

European-Non Finnish (NFE) AF: 9.01e-7 AC: 1 AN: 1109548

Other (OTH) AF: 0.000217 AC: 13 AN: 60034

GnomAD4 genome AF: 0.00121 AC: 184 AN: 152220 Hom.: 2 Cov.: 31 AF XY: 0.00121 AC XY: 90 AN XY: 74408

African (AFR) AF: 0.00424 AC: 176 AN: 41534

American (AMR) AF: 0.000327 AC: 5 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5160

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67996

Other (OTH) AF: 0.00142 AC: 3 AN: 2114

Alfa AF: 0.000469 Hom.: 0

Bravo AF: 0.00141

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	1	Episodic kinesigenic dyskinesia (1)
-	-	1	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	2.8
DANN	Benign	0.69
PhyloP100		-0.69

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

Other links and lift over

dbSNP: rs149260055; hg19: chr16-29824987;