16-29813418-C-T

Variant names:

• chr16-29813418-C-T
• rs1555502665
• NM_145239.3:c.364C>T

Variant summary

Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PVS1 PM2 PP5_Moderate

The NM_145239.3(PRRT2):​c.364C>T​(p.Gln122*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 31)
• Consequence: PRRT2 NM_145239.3 stop_gained
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 0.0750
• 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: Pathogenic. The variant received 12 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 16-29813418-C-T is Pathogenic according to our data. Variant chr16-29813418-C-T is described in ClinVar as Likely_pathogenic. ClinVar VariationId is 1527940.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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRRT2	NM_145239.3	MANE Select	c.364C>T	p.Gln122*	stop_gained	Exon 2 of 4	NP_660282.2
	PRRT2	NM_001256442.2		c.364C>T	p.Gln122*	stop_gained	Exon 2 of 3	NP_001243371.1
	PRRT2	NM_001438121.1		c.364C>T	p.Gln122*	stop_gained	Exon 2 of 3	NP_001425050.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRRT2	ENST00000358758.12	TSL:1 MANE Select	c.364C>T	p.Gln122*	stop_gained	Exon 2 of 4	ENSP00000351608.7
	ENSG00000280893	ENST00000609618.2	TSL:5	n.364C>T		non_coding_transcript_exon	Exon 2 of 6	ENSP00000476774.2
	PRRT2	ENST00000567659.3	TSL:2	c.364C>T	p.Gln122*	stop_gained	Exon 2 of 3	ENSP00000456226.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions as Germline

Significance: Likely pathogenic

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
1	-	-	Infantile convulsions and choreoathetosis (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.60	D
BayesDel_noAF	Pathogenic	0.48
CADD	Pathogenic	34
DANN	Uncertain	0.99
Eigen	Uncertain	0.42
Eigen_PC	Benign	0.12
FATHMM_MKL	Benign	0.28	N
PhyloP100		0.075
Vest4		0.88
GERP RS		2.2

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

Other links and lift over

dbSNP: rs1555502665; hg19: chr16-29824739;