16-29813805-T-C

Variant names:

• chr16-29813805-T-C
• rs11150573
• NM_145239.3:c.751T>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_145239.3(PRRT2):​c.751T>C​(p.Leu251Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.999 in 1,612,408 control chromosomes in the GnomAD database, including 804,209 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. L251L) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.99 (75100 hom., cov: 30)
  • Exomes 𝑓: 1.0 (729109 hom.)
• Consequence: PRRT2 NM_145239.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.238
• Publications: 15 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 16-29813805-T-C is Benign according to our data. Variant chr16-29813805-T-C is described in ClinVar as Benign. ClinVar VariationId is 167544.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.238 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.994 is higher than 0.05.

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.751T>C	p.Leu251Leu	synonymous	Exon 2 of 4	NP_660282.2
	PRRT2	NM_001256442.2		c.751T>C	p.Leu251Leu	synonymous	Exon 2 of 3	NP_001243371.1
	PRRT2	NM_001438121.1		c.751T>C	p.Leu251Leu	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.751T>C	p.Leu251Leu	synonymous	Exon 2 of 4	ENSP00000351608.7
	ENSG00000280893	ENST00000609618.2	TSL:5	n.751T>C		non_coding_transcript_exon	Exon 2 of 6	ENSP00000476774.2
	PRRT2	ENST00000567659.3	TSL:2	c.751T>C	p.Leu251Leu	synonymous	Exon 2 of 3	ENSP00000456226.1

Frequencies

GnomAD3 genomes AF: 0.993 AC: 151073 AN: 152100 Hom.: 75040 Cov.: 30

Gnomad AFR AF: 0.977

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.997

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 1.00

Gnomad NFE AF: 1.00

Gnomad OTH AF: 0.997

GnomAD2 exomes AF: 0.998 AC: 248315 AN: 248724 AF XY: 0.999

Gnomad AFR exome AF: 0.977

Gnomad AMR exome AF: 0.999

Gnomad ASJ exome AF: 1.00

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 1.00

Gnomad NFE exome AF: 1.00

Gnomad OTH exome AF: 1.00

GnomAD4 exome AF: 0.999 AC: 1459191 AN: 1460190 Hom.: 729109 Cov.: 57 AF XY: 0.999 AC XY: 726014 AN XY: 726432

African (AFR) AF: 0.975 AC: 32600 AN: 33420

American (AMR) AF: 0.999 AC: 44392 AN: 44440

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 26004 AN: 26004

East Asian (EAS) AF: 1.00 AC: 39696 AN: 39696

South Asian (SAS) AF: 1.00 AC: 86074 AN: 86076

European-Finnish (FIN) AF: 1.00 AC: 53322 AN: 53322

Middle Eastern (MID) AF: 1.00 AC: 5756 AN: 5756

European-Non Finnish (NFE) AF: 1.00 AC: 1111111 AN: 1111150

Other (OTH) AF: 0.999 AC: 60236 AN: 60326

GnomAD4 genome AF: 0.993 AC: 151192 AN: 152218 Hom.: 75100 Cov.: 30 AF XY: 0.993 AC XY: 73900 AN XY: 74420

African (AFR) AF: 0.977 AC: 40551 AN: 41520

American (AMR) AF: 0.997 AC: 15257 AN: 15300

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 3472 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5154 AN: 5154

South Asian (SAS) AF: 1.00 AC: 4821 AN: 4822

European-Finnish (FIN) AF: 1.00 AC: 10620 AN: 10620

Middle Eastern (MID) AF: 1.00 AC: 294 AN: 294

European-Non Finnish (NFE) AF: 1.00 AC: 68007 AN: 68014

Other (OTH) AF: 0.997 AC: 2104 AN: 2110

Alfa AF: 0.997 Hom.: 51764

Bravo AF: 0.992

Asia WGS AF: 0.999 AC: 3474 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not specified (2)
-	-	1	Episodic kinesigenic dyskinesia (1)
-	-	1	Episodic kinesigenic dyskinesia 1 (1)
-	-	1	Infantile convulsions and choreoathetosis (1)
-	-	1	not provided (1)
-	-	1	Seizures, benign familial infantile, 2 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	8.5
DANN	Benign	0.79
PhyloP100		-0.24
Mutation Taster		=100/0	polymorphism (auto)

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: rs11150573; hg19: chr16-29825126; COSMIC: COSV108056169; COSMIC: COSV108056169;